Alexandre Corthay

• Benimam, Mohamed Mounib; Frafjord, Astri; Corthay, Alexandre Benoit; Lagache, Thibault; Olivo-Marin, Jean Christophe & Meas-Yedid, Vannary (2026). SpatioMap: A Tile-Based Spatial Heatmap Framework for Tumor Microenvironment Heterogeneity in Whole Slide Images. IEEE International Symposium on Biomedical Imaging. ISSN 1945-7928. 2026-April. doi: 10.1109/ISBI61048.2026.11515781. Full text in Research Archive
• Torland, Anne Vold; Geisler, Jürgen; Azimzade, Youness; Frafjord, Astri; Nilsen, Hogne Røed & Buer, Linn [Show all 15 contributors for this article] (2026). Multi-platform analysis of the tumor immune microenvironment associated with breast cancer subtypes. Oncoimmunology. ISSN 2162-4011. 15(1). doi: 10.1080/2162402X.2025.2610535. Full text in Research Archive Show summary

  Breast cancer is genetically and histologically heterogenous, and is influenced by a variety of factors, including the tumor microenvironment (TME). The PAM50 subtypes; Luminal A, Luminal B, Normal-like, Basal-like and Her2-enriched, are associated with different tumor phenotypes and overall survival. The quantity and quality of immune cell infiltration in breast tumors play a key role in cancer development and progression and are associated with survival and treatment response. We used multiplex immunohistochemistry, single-cell RNA sequencing, and two deconvolution algorithms to explore the immune landscape across PAM50 subtypes. Immunostaining of CD3+ T cells, tryptase+ mast cells, CD20+ B cells, CD68+ CD163+ macrophages, and CD66b+ granulocytes revealed marked differences in tumor immune infiltrates according to breast cancer subtypes. Luminal tumors were relatively deprived of T cells and B cells, while exhibiting sparse to moderate amounts of macrophage infiltration. In contrast, Her2-enriched tumors exhibited a moderate immune presence, with sparse to moderate T cell infiltration and moderate infiltration of B cells and macrophages. At the other end of the spectrum, Basal-like tumors stood out for their strikingly rich immune environment and are heavily infiltrated by T cells, B cells, and macrophages. The results from the single-cell and deconvolution analyses confirmed subtype-specific immune microenvironments, which also allowed us to observe increased levels of natural killer (NK) and CD8+ T cells in Her2-enriched and Basal-like subtypes. In conclusion, our findings demonstrate significant differences in the immune tumor microenvironmentbetween the established breast cancer molecular subtypes.

• Hoel, Håvard; Petkowicz, Carmen; Eidsvåg, Victoria; Øynebråten, Inger; Corthay, Alexandre Benoit & Maurer, Juliana Bello Baron [Show all 7 contributors for this article] (2026). Comparative toll-like receptor and dectin-1a activation by structurally diverse plant polysaccharides. Carbohydrate Research. ISSN 0008-6215. 567. doi: 10.1016/j.carres.2026.110003. Full text in Research Archive Show summary

  Naturally derived polysaccharides can activate pattern recognition receptors (PRRs) like Toll-like receptors (TLRs) and Dectin-1, but structure-activity relationships remain unclear. Here, we screened several plant-derived polysaccharides using HEK-Blue™ reporter cells expressing human Toll-like receptor (hTLR) 2, hTLR2/1, hTLR2/6, hTLR3, hTLR4, hTLR5 or hDectin-1a, THP1-Blue™ NF-κB cells and mouse bone marrow-derived macrophages to investigate the correlation between structural features and activity. The polysaccharides included pectins from Gentiana purpurea (GP-AP), Angelica archangelica subsp. archangelica (A-A2-I), Daphne mezereum (DMP-ED-I), Citrullus lanatus (FW), Coffea arabica (CAP) and Citrus sp. (CPA), an arabinogalactan protein (AGP) rich extract from Persea americana (FRAGP), and an arabinoxylan from Livistonia chinensis (LCP). Activation of THP1-Blue™ cells and BMDMs, and interaction with hTLR4 and hTLR2/6 correlated with rhamnogalacturonan-I (RG-I) backbones with galactan, including arabinogalactan-II (AG-II), side chains (GP-AP and DMP-ED-I), and by the presence of AGPs (FRAGP). The presence of 4-O-Me-GlcA in A-A2-I was seemingly negatively correlated with activation of hTLR2/6, despite presence of AG-II structures. The homogalacturonan-rich (HG) polysaccharides investigated in this study, FW, CAP and CPA, did not activate hTLR4 and hTLR2/6, suggesting that HG alone was insufficient for PRR engagement in these models. Several RG-I containing pectins activated hDectin-1a, and higher Mw generally enhanced activity. The AGP and xylose-rich polysaccharides tested in this study did not activate hDectin-1a, and the arabinoxylan LCP was inactive in all assays. None of the polysaccharides activated hTLR3 or hTLR5. In conclusion, several polysaccharides activated multiple PRRs, seemingly associated with presence of RG-I domains with neutral side chains.

• Benimam, Mohamed Mounib; Frafjord, Astri; Corthay, Alexandre Benoit; Lagache, Thibault; Olivo-Marin, Jean Christophe & Meas-Yedid, Vannary (2025). Deep Multitask Learning for Automated Tissue Segmentation and Cell Detection. European Signal Processing Conference. ISSN 2076-1465. p. 1552–1556. doi: 10.23919/EUSIPCO63237.2025.11226185. Full text in Research Archive
• Skourti, Eleni; Vasiliauskaite, Kotryna; Mensali, Nadia; Jabeen, Shakila; Juell, Siri & Øynebråten, Inger [Show all 14 contributors for this article] (2025). Chemoresistant tumor cell secretome potentiates immune suppression in triple negative breast cancer. Breast Cancer Research. ISSN 1465-5411. 27(1). doi: 10.1186/s13058-025-02082-x. Full text in Research Archive Show summary

  Background Chemotherapy is an integral part of the clinical management of triple negative breast cancer (TNBC), however, development of chemoresistance occurs frequently. Tumor sensitivity to treatment is known to be strongly influenced by the immune microenvironment, signifying the predictive potential of immune alterations. How tumor cells that acquire resistance may subsequently modulate the immune microenvironment it is still not well described. Here, we investigated immunomodulation in the context of acquired chemoresistance in TNBC, focusing on the role of the secretome. Methods Bulk RNA sequencing and multiplex cytokine profiling were performed on paclitaxel-resistant and -sensitive isogenic variants of TNBC cells to reveal resistance-associated secretome alterations. The immunomodulatory influence of the tumor cell secretome was investigated by exploring its effect on monocytes, macrophages (MΦs) and T cells derived from healthy blood donors. The influence on the immune cell phenotype and activity was evaluated by measuring molecular markers and performing functional assays. To validate the clinical relevance, we utilized longitudinal -omics data from breast cancer patients refractory to standard chemotherapy in the NeoAva clinical trial. CIBERSORT was applied to transcriptomics data to infer MΦ and T cell abundance in individual tumors upon treatment. To evaluate their association with the secretome profiles, patient-matched serum cytokine data were used. Results The acquisition of chemoresistance was accompanied by enhanced secretion of cytokines. Subsequently, the resistant cell secretome affected the abundance, phenotype and activity of immune cells. Specifically, it potentiated the recruitment of monocytes, facilitated the polarization of MΦs towards the immunosuppressive M2-like phenotype, and attenuated the activation of CD8+ T cells. Data from the NeoAva clinical cohort validated the enrichment of M2 MΦs and/or the depletion of M1 MΦs after treatment in the majority of residual tumors. The MΦ-associated changes counteracted CD8+ T cell abundance and were partially associated with the cytokine-enriched secretome. Conclusion Development of chemoresistance in BC is associated with alterations in the tumor secretome, which impairs immune activation and facilitates immunosuppression. Knowledge on the immune microenvironment in residual tumors after standard chemotherapy could aid in selecting rational treatment options for this group of patients

• Benimam, Mohamed M.; Meas-Yedid, Vannary; Mukherjee, Suvadip; Frafjord, Astri; Corthay, Alexandre Benoit & Lagache, Thibault [Show all 7 contributors for this article] (2025). Statistical analysis of spatial patterns in tumor microenvironment images. Nature Communications. 16(1), p. 1–20. doi: 10.1038/s41467-025-57943-y. Full text in Research Archive Show summary

  Advances in tissue labeling, imaging, and automated cell identification now enable the visualization of immune cell types in human tumors. However, a framework for analyzing spatial patterns within the tumor microenvironment (TME) is still lacking. To address this, we develop Spatiopath, a null-hypothesis framework that distinguishes statistically significant immune cell associations from random distributions. Using embedding functions to map cell contours and tumor regions, Spatiopath extends Ripley’s K function to analyze both cell-cell and cell-tumor interactions. We validate the method with synthetic simulations and apply it to multi-color images of lung tumor sections, revealing significant spatial patterns such as mast cells accumulating near T cells and the tumor epithelium. These patterns highlight differences in spatial organization, with mast cells clustering near the epithelium and T cells positioned farther away. Spatiopath enables a better understanding of immune responses and may help identify biomarkers for patient outcomes.

• Vincze, Orsolya; Minias, Piotr; Corthay, Alexandre Benoit; Colchero, Fernando; Lemaître, Jean-François & Maille, Louise [Show all 19 contributors for this article] (2025). Immunological surveillance against cancer across mammals. Nature Communications. 16(1), p. 1–12. doi: 10.1038/s41467-025-65286-x. Full text in Research Archive Show summary

  Contrary to expectations based on their higher cell numbers, larger and longer-lived species do not face dramatically increased risk of cancer. This strongly suggests that evolution has fashioned natural cancer resistance mechanisms, yet our knowledge remains limited on what these mechanisms might be. The cancer immunological surveillance hypothesis, proposed by Burnet and Thomas in the 1950s, highlights immunity as a key factor determining species-specific cancer resistance. Here we address the original, evolutionary interpretation of this hypothesis by investigating the relationship between cancer mortality risk and markers of efficient antigen presentation. Our results show that the expansion of the MHC class I gene complex, as well as increased selection for diversity at these genes is associated with sharply decreasing cancer mortality risk across mammals. This suggests that the efficient presentation of diverse peptides in somatic cells is important for cancer suppression across mammals, providing pioneering evidence that supports the cancer immunosurveillance hypothesis across species.

• Wold, Christian Winther; Christopoulos, Panagiotis; Arias, Maykel; Dzovor, Deborah Elikplim; Øynebråten, Inger & Corthay, Alexandre Benoit [Show all 7 contributors for this article] (2024). Fungal polysaccharides from Inonotus obliquus are agonists for Toll-like receptors and induce macrophage anti-cancer activity. Communications Biology. 7. doi: 10.1038/s42003-024-05853-y. Full text in Research Archive Show summary

  Fungal polysaccharides can exert immunomodulating activity by triggering pattern recognition receptors (PRRs) on innate immune cells such as macrophages. Here, we evaluate six polysaccharides isolated from the medicinal fungus Inonotus obliquus for their ability to activate mouse and human macrophages. We identify two water-soluble polysaccharides, AcF1 and AcF3, being able to trigger several critical antitumor functions of macrophages. AcF1 and AcF3 activate macrophages to secrete nitric oxide and the pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Combined with interferon-γ, the fungal polysaccharides trigger high production of IL-12p70, a central cytokine for antitumor immunity, and induce macrophage-mediated inhibition of cancer cell growth in vitro and in vivo. AcF1 and AcF3 are strong agonists of the PRRs Toll-like receptor 2 (TLR2) and TLR4, and weak agonists of Dectin-1. In comparison, two prototypical particulate β-glucans, one isolated from I. obliquus and one from Saccharomyces cerevisiae (zymosan), are agonists for Dectin-1 but not TLR2 or TLR4, and are unable to trigger anti-cancer functions of macrophages. We conclude that the water-soluble polysaccharides AcF1 and AcF3 from I. obliquus have a strong potential for cancer immunotherapy by triggering multiple PRRs and by inducing potent anti-cancer activity of macrophages.

• Gilmour, Brian Christopher; Corthay, Alexandre Benoit & Øynebråten, Inger (2024). High production of IL-12 by human dendritic cells stimulated with combinations of pattern-recognition receptor agonists. npj Vaccines. 9:83(1), p. 1–12. doi: 10.1038/s41541-024-00869-1. Full text in Research Archive Show summary

  The cytokine IL-12p70 is crucial for T helper 1 (Th1) polarization and the generation of type 1 immunity required to fight cancer and pathogens. Therefore, strategies to optimize the production of IL-12p70 by human dendritic cells (DCs) may significantly improve the efficacy of vaccines and immunotherapies. However, the rules governing the production of IL-12p70 remain obscure. Here, we stimulated pattern recognition receptors (PRRs) representing five families of PRRs, to evaluate their ability to elicit high production of IL-12p70 by monocyte-derived DCs. We used ten well-characterized agonists and stimulated DCs in vitro with either single agonists or 27 different combinations. We found that poly(I:C), which engages the RNA-sensing PRRs TLR3 and MDA5, and LPS which stimulates TLR4, were the only agonists that could elicit notable IL-12p70 production when used as single ligands. We identified six different combinations of PRR agonists, all containing either the TLR3/MDA5 agonist poly(I:C) or the TLR7/8 agonist R848, that could synergize to elicit high production of IL-12p70 by human DCs. Five of the six combinations also triggered high production of the antiviral and antitumor cytokine IFNβ. Overall, the tested PRR ligands could be divided into three groups depending on whether they triggered production of both IL-12p70 and IFNβ, only one of the two, or neither. Thus, combinations of PRR agonists were found to increase the production of IL-12p70 by human DCs in a synergistic manner, and we identified six PRR agonist combinations that may represent strong adjuvant candidates, in particular for therapeutic cancer vaccines.

• Mariampillai, Adrian Eek; Hauge, Sissel; Øynebråten, Inger; Rødland, Gro Elise; Corthay, Alexandre Benoit & Syljuåsen, Randi G. (2022). Caspase activation counteracts interferon signaling after G2 checkpoint abrogation by ATR inhibition in irradiated human cancer cells. Frontiers in Oncology. 12, p. 1–14. doi: 10.3389/fonc.2022.981332. Full text in Research Archive Show summary

  Recent studies suggest that inhibition of the ATR kinase can potentiate radiation-induced antitumor immune responses, but the extent and mechanisms of such responses in human cancers remain scarcely understood. We aimed to assess whether the ATR inhibitors VE822 and AZD6738, by abrogating the G2 checkpoint, increase cGAS-mediated type I IFN response after irradiation in human lung cancer and osteosarcoma cell lines. Supporting that the checkpoint may prevent IFN induction, radiation-induced IFN signaling declined when the G2 checkpoint arrest was prolonged at high radiation doses. G2 checkpoint abrogation after co-treatment with radiation and ATR inhibitors was accompanied by increased radiation-induced IFN signaling in four out of five cell lines tested. Consistent with the hypothesis that the cytosolic DNA sensor cGAS may detect DNA from ruptured micronuclei after G2 checkpoint abrogation, cGAS co-localized with micronuclei, and depletion of cGAS or STING abolished the IFN responses. Contrastingly, one lung cancer cell line showed no increase in IFN signaling despite irradiation and G2 checkpoint abrogation. This cell line showed a higher level of the exonuclease TREX1 than the other cell lines, but TREX1 depletion did not enhance IFN signaling. Rather, addition of a pan-caspase inhibitor restored the IFN response in this cell line and also increased the responses in the other cell lines. These results show that treatment-induced caspase activation can suppress the IFN response after co-treatment with radiation and ATR inhibitors. Caspase activation thus warrants further consideration as a possible predictive marker for lack of IFN signaling.

• Corthay, Alexandre; Bakacs, Tibor; Thangavelu, Govindarajan & Anderson, Colin C. (2021). Tackling cancer cell dormancy: Insights from immune models, and transplantation. Seminars in Cancer Biology. ISSN 1044-579X. 78, p. 5–16. doi: 10.1016/j.semcancer.2021.02.002. Full text in Research Archive Show summary

  Disseminated non-dividing (dormant) cancer cells as well as those in equilibrium with the immune response remain the major challenge for successful treatment of cancer. The equilibrium between disseminated dormant cancer cells and the immune system is reminiscent of states that can occur during infection or allogeneic tissue and cell transplantation. We discuss here the major competing models of how the immune system achieves a self nonself discrimination (pathogen/danger patterns, quorum, and coinhibition/tuning models), and suggest that taking advantage of a combination of the proposed mechanisms in each model may lead to increased efficacy in tackling cancer cell dormancy.

• Christopoulos, Panagiotis; Grigalavicius, Mantas; Corthay, Alexandre; Berg, Kristian & Theodossiou, Theodossis (2021). Reactive Species from Two-Signal Activated Macrophages Interfere with Their Oxygen Consumption Measurements. Antioxidants. 10:1149(7), p. 1–12. doi: 10.3390/antiox10071149. Full text in Research Archive Show summary

  Metabolic modulation of macrophage activation has emerged as a promising strategy lately in immunotherapeutics. However, macrophages have a broad spectrum of functions and thus, understanding the exact metabolic changes that drive a particular immune response, is of major importance. In our previous work, we have reported a key role of nitric oxide (NO●) in two(2)-signal activated macrophages [M(2-signals)]. Further characterization using metabolic analysis in intact cells, showed that the basal and maximal respiration levels of M(2-signals) were comparable, with cells being unresponsive to the injections-inducd mitochondrial stress. Here, we show that excessive NO● secretion by the M(2-signals) macrophages, interferes with the oxygen (O2) consumption measurements on cells using the seahorse metabolic analyzer. This is attributed mainly to the consumption of ambient oxygen by NO● to form NO2− and/or NO3− but also to the reduction of O2 to superoxide anion (O2●−) by stray electrons from the electron transport chain, leading to the formation of peroxynitrite (ONOO−). We found that reactive species-donors in the absence of cells, produce comparable oxygen consumption rates (OCR) with M(2-signals) macrophages. Furthermore, inhibition of NO● production, partly recovered the respiration of activated macrophages, while external addition of NO● in non-activated macrophages downregulated their OCR levels. Our findings are crucial for the accurate metabolic characterization of cells, especially in cases where reactive nitrogen or oxygen species are produced in excess.

• Frafjord, Astri; Buer, Linn; Hammarström, Clara Louise; Aamodt, Henrik; Woldbæk, Per R & Brustugun, Odd Terje [Show all 9 contributors for this article] (2021). The Immune Landscape of Human Primary Lung Tumors Is Th2 Skewed. Frontiers in Immunology. 12:764596, p. 1–15. doi: 10.3389/fimmu.2021.764596. Full text in Research Archive Show summary

  Tumor-specific T helper (Th) cells have a central role in the immune response against cancer. However, there exist distinct Th cell subsets with very different and antagonizing properties. Some Th subsets such as Th1 protect against cancer, while others (Th2, T regulatory/Treg) are considered detrimental or of unknown significance (T follicular helper/Tfh, Th17). The Th composition of human solid tumors remains poorly characterized. Therefore, we established a four-color multiplex chromogenic immunohistochemical assay for detection of Th1, Th2, Th17, Tfh and Treg cells in human tumor sections. The method was used to analyze resected primary lung tumors from 11 patients with non-small cell lung cancer (NSCLC). Four microanatomical regions were investigated: tumor epithelium, tumor stroma, peritumoral tertiary lymphoid structures (TLS) and non-cancerous distal lung tissue. In tumor epithelium and stroma, most CD4 + T cells identified had either a Th2 (GATA-3 + CD3 + CD8 - ) or Treg (FOXP3 + CD3 + CD8 - ) phenotype, whereas only low numbers of Th1, Th17, and Tfh cells were observed. Similarly, Th2 was the most abundant Th subset in TLS, followed by Treg cells. In sharp contrast, Th1 was the most frequently detected Th subset in non-cancerous lung tissue from the same patients. A higher Th1:Th2 ratio in tumor stroma was found to be associated with increased numbers of intratumoral CD8 + T cells. The predominance of Th2 and Treg cells in both tumor stroma and tumor epithelium was consistent for all the 11 patients investigated. We conclude that human primary NSCLC tumors are Th2-skewed and contain numerous Treg cells. If human tumors are Th2-skewed, as our data in NSCLC suggest, reprogramming the type of immune response from a detrimental Th2 to a beneficial Th1 may be critical to increase the response rate of immunotherapy.

• Frafjord, Astri; Skarshaug, Renate; Hammarström, Clara Louise; Stankovic, Branislava; Dorg, Linda Trobe & Aamodt, Henrik [Show all 11 contributors for this article] (2020). Antibody combinations for optimized staining of macrophages in human lung tumours. Scandinavian Journal of Immunology. ISSN 0300-9475. 92:e12889(1), p. 1–24. doi: 10.1111/sji.12889. Full text in Research Archive Show summary

  The analysis of tumour‐associated macrophages (TAMs) has a high potential to predict cancer recurrence and response to immunotherapy. However, the heterogeneity of TAMs poses a challenge for quantitative and qualitative measurements. Here, we critically evaluated by immunohistochemistry and flow cytometry two commonly used pan‐macrophage markers (CD14 and CD68) as well as some suggested markers for tumour‐promoting M2 macrophages (CD163, CD204, CD206 and CD209) in human non–small cell lung cancer (NSCLC). Tumour, non‐cancerous lung tissue and blood were investigated. For immunohistochemistry, CD68 was confirmed to be a useful pan‐macrophage marker although careful selection of antibody was found to be critical. The widely used anti‐CD68 antibody clone KP‐1 stains both macrophages and neutrophils, which is problematic for TAM quantification because lung tumours contain many neutrophils. For TAM counting in tumour sections, we recommend combined labelling of CD68 with a cell membrane marker such as CD14, CD163 or CD206. In flow cytometry, the commonly used combination of CD14 and HLA‐DR was found to not be optimal because some TAMs do not express CD14. Instead, combined staining of CD68 and HLA‐DR is preferable to gate all TAMs. Concerning macrophage phenotypic markers, the scavenger receptor CD163 was found to be expressed by a substantial fraction (50%‐86%) of TAMs with a large patient‐to‐patient variation. Approximately 50% of TAMs were positive for CD206. Surprisingly, there was no clear overlap between CD163 and CD206 positivity, and three distinct TAM sub‐populations were identified in NSCLC tumours: CD163+CD206+, CD163+CD206− and CD163−CD206−. This work should help develop macrophage‐based prognostic tools for cancer.

• Waaler, Jo; Mygland, Line; Tveita, Anders Aune; Strand, Martin Frank; Solberg, Nina & Olsen, Petter Angell [Show all 19 contributors for this article] (2020). Tankyrase inhibition sensitizes melanoma to PD-1 immune checkpoint blockade in syngeneic mouse models. Communications Biology. 3. doi: 10.1038/s42003-020-0916-2. Full text in Research Archive Show summary

  The development of immune checkpoint inhibitors represents a major breakthrough in cancer therapy. Nevertheless, a substantial number of patients fail to respond to checkpoint pathway blockade. Evidence for WNT/β-catenin signaling-mediated immune evasion is found in a subset of cancers including melanoma. Currently, there are no therapeutic strategies available for targeting WNT/β-catenin signaling. Here we show that a specific small-molecule tankyrase inhibitor, G007-LK, decreases WNT/β-catenin and YAP signaling in the syngeneic murine B16-F10 and Clone M-3 melanoma models and sensitizes the tumors to anti-PD-1 immune checkpoint therapy. Mechanistically, we demonstrate that the synergistic effect of tankyrase and checkpoint inhibitor treatment is dependent on loss of β-catenin in the tumor cells, anti-PD-1-stimulated infiltration of T cells into the tumor and induction of an IFNγ- and CD8+ T cell-mediated anti-tumor immune response. Our study uncovers a combinatorial therapeutical strategy using tankyrase inhibition to overcome β-catenin-mediated resistance to immune checkpoint blockade in melanoma.

• Stankovic, Branislava; Aamodt, Henrik; Bjørhovde, Heidi Anine Korsmo; Müller, Elisabeth; Hammarström, Clara Louise & Brustugun, Odd Terje [Show all 9 contributors for this article] (2020). The immune microenvironment in typical carcinoid lung tumour, a brief report of four cases. Scandinavian Journal of Immunology. ISSN 0300-9475. 92:e12893(2), p. 1–12. doi: 10.1111/sji.12893. Full text in Research Archive Show summary

  Pulmonary typical carcinoid (TC) is a low‐grade, rare lung cancer of neuroendocrine origin. Currently, there is very little information available about the immune cell composition in TC tumours. Here, we analysed by flow cytometry resected tumours from four never‐smoker female patients with TC. Twelve distinct immune cell types were identified in TC tumours. The most abundant immune cells were CD8+ T cells, CD4+ T cells, B cells and macrophages, which represented 19.8%, 17.7%, 11.5% and 11% of all tumour‐infiltrating CD45+ leucocytes, respectively. Natural killer (NK) cells (8.8%) and neutrophils (3.9%) were also common. Three types of dendritic cells (DCs) were identified (plasmacytoid DCs, CD1c DCs, and CD141 DCs) which together constituted 1.4% of all immune cells in TC tumours. Small populations of basophils (1.2%), mast cells (0.8%) and eosinophils (0.6%) were also present. Notably, the percentage of leucocytes (of all living cells) was much lower in TC tumours compared to high‐grade non‐small cell lung cancer (NSCLC) tumours and also compared to non‐cancerous lung tissue. We conclude that TC tumours are relatively non‐inflammatory, although the immune landscape was found to be very complex.

• Wold, Christian Winther; Kjeldsen, Christian; Corthay, Alexandre Benoit; Rise, Frode; Christensen, Bjørn E. & Duus, Jens Øllgaard [Show all 7 contributors for this article] (2018). Structural characterization of bioactive heteropolysaccharides from the medicinal fungus Inonotus obliquus (Chaga). Carbohydrate Polymers. ISSN 0144-8617. 185, p. 40–40. doi: 10.1016/j.carbpol.2017.12.041. Full text in Research Archive
• Haabeth, Ole Audun; Fauskanger, Marte; Manzke, Melanie; Lundin, Katrin; Corthay, Alexandre & Bogen, Bjarne [Show all 7 contributors for this article] (2018). CD4+ T-cell–Mediated Rejection of MHC Class II–Positive Tumor Cells Is Dependent on Antigen Secretion and Indirect Presentation on Host APCs. Cancer Research. ISSN 0008-5472. 78(16), p. 4573–4585. doi: 10.1158/0008-5472.CAN-17-2426. Full text in Research Archive
• Müller, Elisabeth; Speth, Martin; Christopoulos, Panagiotis; Lunde, Anna; Avdagic, Ajna & Øynebråten, Inger [Show all 7 contributors for this article] (2018). Both type I and type II interferons can activate antitumor M1 macrophages when combined with TLR stimulation. Frontiers in Immunology. 9, p. 1–16. doi: 10.3389/fimmu.2018.02520. Full text in Research Archive Show summary

  Triggering or enhancing antitumor activity of tumor-associated macrophages is an attractive strategy for cancer treatment. We have previously shown that the cytokine interferon-γ (IFN-γ), a type II IFN, could synergize with toll-like receptor (TLR) agonists for induction of antitumor M1 macrophages. However, the toxicity of IFN-γ limits its clinical use. Here, we investigated whether the less toxic type I IFNs, IFN-α, and IFN-β, could potentially replace IFN-γ for induction of antitumor M1 macrophages. We measured in vitro the ability of type I and II IFNs to synergize with TLR agonists for transcription of inducible nitric oxide synthase (iNOS) mRNA and secretion of nitric oxide (NO) by mouse bone marrow-derived macrophages (BMDMs). An in vitro growth inhibition assay was used to measure both cytotoxic and cytostatic activity of activated macrophages against Lewis lung carcinoma (LLC) cancer cells. We found that both type I and II IFNs could synergize with TLR agonists in inducing macrophage-mediated inhibition of cancer cell growth, which was dependent on NO. The ability of high dose lipopolysaccharide (LPS) to induce tumoricidal activity in macrophages in the absence of IFN-γ was shown to depend on induction of autocrine type I IFNs. Antitumor M1 macrophages could also be generated in the absence of IFN-γ by a combination of two TLR ligands when using the TLR3 agonist poly(I:C) which induces autocrine type I IFNs. Finally, we show that encapsulation of poly(I:C) into nanoparticles improved its potency to induce M1 macrophages up to 100-fold. This study reveals the potential of type I IFNs for activation of antitumor macrophages and indicates new avenues for cancer immunotherapy based on type I IFN signaling, including combination of TLR agonists.

• Stankovic, Branislava; Bjørhovde, Heidi Anine Korsmo; Skarshaug, Renate; Aamodt, Henrik; Frafjord, Astri & Müller, Elisabeth [Show all 14 contributors for this article] (2018). Immune Cell Composition in Human Non-small Cell Lung Cancer. Frontiers in Immunology. 9. doi: 10.3389/fimmu.2018.03101. Full text in Research Archive Show summary

  Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death in the world. Immunological analysis of the tumor microenvironment (immunoscore) shows great promise for improved prognosis and prediction of response to immunotherapy. However, the exact immune cell composition in NSCLC remains unclear. Here, we used flow cytometry to characterize the immune infiltrate in NSCLC tumors, non-cancerous lung tissue, regional lymph node, and blood. The cellular identity of >95% of all CD45+ immune cells was determined. Thirteen distinct immune cell types were identified in NSCLC tumors. T cells dominated the lung cancer landscape (on average 47% of all CD45+ immune cells). CD4+ T cells were the most abundant T cell population (26%), closely followed by CD8+ T cells (22%). Double negative CD4−CD8− T cells represented a small fraction (1.4%). CD19+ B cells were the second most common immune cell type in NSCLC tumors (16%), and four different B cell sub-populations were identified. Macrophages and natural killer (NK) cells composed 4.7 and 4.5% of the immune cell infiltrate, respectively. Three types of dendritic cells (DCs) were identified (plasmacytoid DCs, CD1c+ DCs, and CD141+ DCs) which together represented 2.1% of all immune cells. Among granulocytes, neutrophils were frequent (8.6%) with a high patient-to- patient variability, while mast cells (1.4%), basophils (0.4%), and eosinophils (0.3%) were less common. Across the cohort of patients, only B cells showed a significantly higher representation in NSCLC tumors compared to the distal lung. In contrast, the percentages of macrophages and NK cells were lower in tumors than in non-cancerous lung tissue. Furthermore, the fraction of macrophages with high HLA-DR expression levels was higher in NSCLC tumors relative to distal lung tissue. To make the method readily accessible, antibody panels and flow cytometry gating strategy used to identify the various immune cells are described in detail. This work should represent a useful resource for the immunomonitoring of patients with NSCLC.

• Müller, Elisabeth; Christopoulos, Panagiotis; Halder, Sanjib; Lunde, Anna; Beraki, Kahsai & Speth, Martin [Show all 8 contributors for this article] (2017). Toll-like receptor ligands and interferon-gamma synergize for induction of antitumor M1 macrophages. Frontiers in Immunology. 8. doi: 10.3389/fimmu.2017.01383. Full text in Research Archive Show summary

  Tumor-associated macrophages may either promote or suppress tumor growth depending on their activation status. Interferon-γ (IFN-γ) has been identified as a key factor for inducing tumoricidal M1 phenotype in macrophages. However, it remains unclear whether IFN-γ is sufficient or if additional stimuli are required. Here, we tested IFN-γ and a panel of toll-like receptor (TLR) agonists for the ability to activate murine macrophages toward a tumoricidal M1 phenotype. The following TLR ligands were used: TLR1/TLR2 agonist Pam3CSK4, TLR2/TLR6 agonist lipotechoic acid, TLR3 agonist poly(I:C), TLR4 agonist lipopolysaccharide (LPS), TLR5 agonist flagellin, TLR7 agonist CL264, and TLR9 agonist CpG. We used an in vitro growth inhibition assay to measure both cytotoxic and cytostatic activity of mouse macrophages against Lewis lung carcinoma (LLC) and MOPC315 plasmacytoma tumor cells. Production of nitric oxide (NO) and cytokines by activated macrophages was quantified. We found that IFN-γ alone was not able to render macrophages tumoricidal. Similarly, macrophage activation with single TLR agonists was inefficient. In sharp contrast, IFN-γ was shown to synergize with TLR agonists for induction of macrophage tumoricidal activity and production of both NO and pro-inflammatory cytokines (TNF-α, IL-12p40, and IL-12p70). Furthermore, IFN-γ was shown to suppress macrophage IL-10 secretion induced by TLR agonists. NO production was necessary for macrophage tumoricidal activity. We conclude that two signals from the microenvironment are required for optimal induction of antitumor M1 macrophage phenotype. Combination treatment with IFN-γ and TLR agonists may offer new avenues for macrophage-based cancer immunotherapy.

• Speth, Martin; Repnik, Urska; Müller, Elisabeth; Spanier, Julia; Kalinke, Ulrich & Corthay, Alexandre [Show all 7 contributors for this article] (2017). Poly(I:C)-Encapsulating Nanoparticles Enhance Innate Immune Responses to the Tuberculosis Vaccine Bacille Calmette-Guerin (BCG) via Synergistic Activation of Innate Immune Receptors. Molecular Pharmaceutics. ISSN 1543-8384. 14(11), p. 4098–4112. doi: 10.1021/acs.molpharmaceut.7b00795. Full text in Research Archive
• Kurena, Baiba; Müller, Elisabeth; Christopoulos, Panagiotis; Johnsen, Ingvild Bjellmo; Stankovic, Branislava & Øynebråten, Inger [Show all 8 contributors for this article] (2017). Generation and Functional In Vitro Analysis of Semliki Forest Virus Vectors Encoding TNF-α and IFN-γ. Frontiers in Immunology. 8. doi: 10.3389/fimmu.2017.01667. Full text in Research Archive Show summary

  Cytokine gene delivery by viral vectors is a promising novel strategy for cancer immunotherapy. Semliki Forest virus (SFV) has many advantages as a delivery vector, including the ability to (i) induce p53-independent killing of tumor cells via apoptosis, (ii) elicit a type-I interferon (IFN) response, and (iii) express high levels of the transgene. SFV vectors encoding cytokines such as interleukin (IL)-12 have shown promising therapeutic responses in experimental tumor models. Here, we developed two new recombinant SFV vectors encoding either murine tumor necrosis factor-α (TNF-α) or murine interferon-γ (IFN-γ), two cytokines with documented immunostimulatory and antitumor activity. The SFV vector showed high infection rate and cytotoxicity in mouse and human lung carcinoma cells in vitro. By contrast, mouse and human macrophages were resistant to infection with SFV. The recombinant SFV vectors directly inhibited mouse lung carcinoma cell growth in vitro, while exploiting the cancer cells for production of SFV vector-encoded cytokines. The functionality of SFV vector-derived TNF-α was confirmed through successful induction of cell death in TNF-α-sensitive fibroblasts in a concentration-dependent manner. SFV vector-derived IFN-γ activated macrophages toward a tumoricidal phenotype leading to suppressed Lewis lung carcinoma cell growth in vitro in a concentration-dependent manner. The ability of SFV to provide functional cytokines and infect tumor cells but not macrophages suggests that SFV may be very useful for cancer immunotherapy employing tumor-infiltrating macrophages.

• Wold, Christian Winther; Kjeldsen, Christian; Corthay, Alexandre; Rise, Frode; Christensen, Bjørn E. & Duus, Jens Øllgaard [Show all 7 contributors for this article] (2017). Structural characterization of bioactive heteropolysaccharides from the medicinal fungus Inonotus obliquus (Chaga). Carbohydrate Polymers. ISSN 0144-8617. 185, p. 27–40. doi: 10.1016/j.carbpol.2017.12.041. Full text in Research Archive Show summary

  The aim of this paper was to perform a comprehensive characterization of polysaccharides isolated from the interior (IOI) and exterior (IOE) parts of the fungus Inonotus obliquus. Pre-extraction with DCM and MeOH, followed by water and alkali extraction and ethanol precipitation gave two water extracts and two alkali extracts. Neutral and acidic polysaccharide fractions were obtained after anion-exchange chromatography of the water extracts. The neutral polysaccharides (60–73 kDa) were heterogeneous and branched and consisted of a (1 → 3)-linked β-Glc backbone with (1 → 6)-linked kinks in the chain at approximately every fifth residue, with branches of (1 → 6)-linked β-Glc in addition to substantial amounts of (1 → 6)-linked α-Gal with 3-O-methylation at about every third Gal residue. The acidic polysaccharide fractions (10–31 kDa) showed similar structural motifs as the neutral fractions differing mainly by the presence of (1 → 4)-linked α-GalA and α-GlcA. β-Xyl, α-Man and α-Rha were also present in varying amounts in all fractions. No major structural differences between the IOI and IOE fractions were observed. An alkaline polysaccharide fraction (>450 kDa) was obtained from the IOI alkali extract, and consisted mainly of (1 → 3)- and (1 → 6)-linked β-Glc and (1 → 4)-linked β-Xyl. Several of the fractions showed in vitro immunomodulatory effect by increasing NO production in the murine macrophage and dendritic cell lines J774.A1 and D2SC/1. Most fractions managed to increase NO production only at the highest concentration tested (100 μg/ml), while the neutral fraction IOE-WN activated potent NO production at 10 μg/ml and was considered the most promising immunomodulating fraction in this study.

• Obando, Daniel F. González; Frafjord, Astri; Øynebråten, Inger; Corthay, Alexandre; Olivo-Marin, Jean-Christophe & Meas-Yedid, Vannary (2017). Multi-staining registration of large histology images. IEEE International Symposium on Biomedical Imaging. ISSN 1945-7928. p. 345–348. doi: 10.1109/ISBI.2017.7950534. Full text in Research Archive
• Christopoulos, Panagiotis; Corthay, Alexandre & Koutsilieris, Michael (2017). Aiming for the Insulin-like Growth Factor-1 system in breast cancer therapeutics. Cancer Treatment Reviews. ISSN 0305-7372. 63, p. 79–95. doi: 10.1016/j.ctrv.2017.11.010. Full text in Research Archive
• Anderson, Colin C.; Bretscher, Peter; Corthay, Alexandre; Dembic, Zlatko; Havele, Calliopi & Nagy, Zoltan A. [Show all 7 contributors for this article] (2017). Immunological Tolerance. Part I of a Report of a Workshop on Foundational Concepts of Immune Regulation. Scandinavian Journal of Immunology. ISSN 0300-9475. 85(2), p. 84–94. doi: 10.1111/sji.12500. Full text in Research Archive
• Bretscher, Peter; Corthay, Alexandre; Anderson, Colin C.; Dembic, Zlatko; Havele, Calliopi & Nagy, Zoltan A. [Show all 7 contributors for this article] (2017). Immune Class Regulation and Its Medical Significance Part II of a Report of a Workshop on Foundational Concepts of Immune Regulation. Scandinavian Journal of Immunology. ISSN 0300-9475. 85(4), p. 242–250. doi: 10.1111/sji.12525. Full text in Research Archive Show summary

  We discussed different proposals for how the nature of the Th1/Th2 phenotype of an immune response is determined, and favoured one, the Threshold Hypothesis, as plausible and so useful as the basis for further discussions. The activation of a target CD4 T cell can be facilitated by helper CD4 T cells when the CD4 T cells interact via an antigen-presenting cell. The Threshold Hypothesis states that tentative and robust antigen-mediated CD4 T cell cooperation results in the target CD4 T cell, respectively giving rise, upon activation, to Th1 and Th2 cells. We primarily discussed four topics. We briefly discussed in the background section certain limitations of the Th1/Th2 paradigm in understanding immune class regulation, and the remarkable anti-inflammatory properties of human IgG4 antibody. Secondly, we assessed the role of class II MHC molecules in determining the number of mature CD4 T cells and so affecting the Th1/Th2 phenotype of immune responses. We also discussed the controversial role of CD8 T cells in affecting the Th1/Th2 phenotype of responses to MHC and other antigens, and the potential role of their relative scarcity in neonates in biasing responses towards an antibody, Th2 mode. Lastly, we examined the regulation of the Th1/Th2 phenotype of both primary and ongoing immune responses in the context of the intriguing proposal that antigen initially generates different classes/subclasses of immunity and then selects, by a feedback mechanism, the most effective class. We found this interesting idea difficult to reconcile with various observations.

• Lorvik, Kristina Berg; Hammarström, Clara Louise; Fauskanger, Marte; Haabeth, Ole Audun; Zangani, Michael M & Haraldsen, Guttorm [Show all 8 contributors for this article] (2016). Adoptive transfer of tumor-specific Th2 cells eradicates tumors by triggering an in situ inflammatory immune response. Cancer Research. ISSN 0008-5472. 76(23), p. 6864–6876. doi: 10.1158/0008-5472.CAN-16-1219. Full text in Research Archive
• Joly-Battaglini, Albane; Hammarström, Clara Louise; Stankovic, Branislava; Aamodt, Henrik; Stjärne, Johan Folke Håkan & Brustugun, Odd Terje [Show all 9 contributors for this article] (2016). Rituximab efficiently depletes B cells in lung tumors and normal lung tissue. F1000. 5. doi: 10.12688/f1000research.7599.1. Full text in Research Archive
• Andersen, Aram Nikolai; Landsverk, Ole J. B.; Simonsen, Anne; Bogen, Bjarne; Corthay, Alexandre & Øynebråten, Inger (2016). Coupling of HIV-1 antigen to the selective autophagy receptor SQSTM1/p62 promotes T-cell-mediated immunity. Frontiers in Immunology. 7. doi: 10.3389/fimmu.2016.00167. Full text in Research Archive Show summary

  Vaccines aiming to promote T-cell-mediated immune responses have so far showed limited efficacy, and there is a need for novel strategies. Studies indicate that autophagy plays an inherent role in antigen processing and presentation for CD4+ and CD8+ T cells. Here, we report a novel vaccine strategy based on fusion of antigen to the selective autophagy receptor sequestosome 1 (SQSTM1)/p62. We hypothesized that redirection of vaccine antigen from proteasomal degradation into the autophagy pathway would increase the generation of antigen-specific T cells. A hybrid vaccine construct was designed in which the antigen is fused to the C-terminus of p62, a signaling hub, and a receptor that naturally delivers ubiquitinated cargo for autophagic degradation. Fusion of the human immunodeficiency virus-1 antigen Gagp24 to p62 resulted in efficient antigen delivery into the autophagy pathway. Intradermal immunization of mice revealed that, in comparison to Gagp24 delivered alone, fusion to p62 enhanced the number of Gagp24-specific interferon-γ-producing T cells, including CD8+ T cells. The strategy may also have the potential to modulate the antigenic peptide repertoire. Because p62 and autophagy are highly conserved between species, we anticipate this strategy to be a candidate for the development of T-cell-based vaccines in humans.

• Haabeth, Ole Audun; Lorvik, Kristina Berg; Yagita, Hideo; Bogen, Bjarne & Corthay, Alexandre (2016). Interleukin-1 is required for cancer eradication mediated by tumor-specific Th1 cells. Oncoimmunology. ISSN 2162-4011. 5(1). doi: 10.1080/2162402X.2015.1039763. Full text in Research Archive
• Haabeth, Ole Audun; Tveita, Anders; Fauskanger, Marte Hotvedt; Schjesvold, Fredrik Hellem; Lorvik, Kristina Berg & Hofgaard, Peter Olaf [Show all 11 contributors for this article] (2014). How do CD4+ T cells detect and eliminate tumor cells that either lack or express MHC class II molecules? Frontiers in Immunology. 5:174. doi: 10.3389/fimmu.2014.00174. Full text in Research Archive Show summary

  CD4+ T cells contribute to tumor eradication, even in the absence of CD8+ T cells. Cytotoxic CD4+ T cells can directly kill MHC class II positive tumor cells. More surprisingly, CD4+ T cells can indirectly eliminate tumor cells that lack MHC class II expression. Here, we review the mechanisms of direct and indirect CD4+ T cell-mediated elimination of tumor cells. An emphasis is put on T cell receptor (TCR) transgenic models, where anti-tumor responses of naïve CD4+ T cells of defined specificity can be tracked. Some generalizations can tentatively be made. For both MHCIIPOS and MHCIINEG tumors, presentation of tumor-specific antigen by host antigen-presenting cells (APCs) appears to be required for CD4+ T cell priming. This has been extensively studied in a myeloma model (MOPC315), where host APCs in tumor-draining lymph nodes are primed with secreted tumor antigen. Upon antigen recognition, naïve CD4+ T cells differentiate into Th1 cells and migrate to the tumor. At the tumor site, the mechanisms for elimination of MHCIIPOS and MHCIINEG tumor cells differ. In a TCR-transgenic B16 melanoma model, MHCIIPOS melanoma cells are directly killed by cytotoxic CD4+ T cells in a perforin/granzyme B-dependent manner. By contrast, MHCIINEG myeloma cells are killed by IFN-γ stimulated M1-like macrophages. In summary, while the priming phase of CD4+ T cells appears similar for MHCIIPOS and MHCIINEG tumors, the killing mechanisms are different. Unresolved issues and directions for future research are addressed.

• Corthay, Alexandre (2014). Does the immune system naturally protect against cancer? Frontiers in Immunology. 5(MAY). doi: 10.3389/fimmu.2014.00197. Full text in Research Archive
• Lorvik, Kristina Berg; Haabeth, Ole Audun; Clancy, Trevor; Bogen, Bjarne & Corthay, Alexandre (2013). Molecular profiling of tumor-specific T(H)1 cells activated in vivo. Oncoimmunology. ISSN 2162-4011. 2(5:e24383). doi: 10.4161/onci.24383. Full text in Research Archive
• Haabeth, Ole Audun; Bogen, Bjarne & Corthay, Alexandre (2012). A model for cancer-suppressive inflammation. Oncoimmunology. ISSN 2162-4011. 1(7), p. 1146–1155. doi: 10.4161/onci.21542. Full text in Research Archive
• Berge, Tone; Grønningsæter, Ingrid Helene; Lorvik, Kristina Berg; Abrahamsen, Greger; Granum, Stine & Gjerstad, Vibeke Sundvold [Show all 9 contributors for this article] (2012). SH2D2A Modulates T Cell Mediated Protection to a B Cell Derived Tumor in Transgenic Mice. PLOS ONE. 7(10). doi: 10.1371/journal.pone.0048239. Full text in Research Archive
• Haabeth, Ole Audun; Lorvik, Kristina Berg; Hammarstrøm, Clara Louise; Donaldson, Ian Matthew; Haraldsen, Guttorm & Bogen, Bjarne [Show all 7 contributors for this article] (2011). Inflammation driven by tumour-specific Th1 cells protects against B-cell cancer. Nature Communications. 2. doi: 10.1038/ncomms1239. Full text in Research Archive
• Corthay, Alexandre; Lorvik, Kristina Berg & Bogen, Bjarne (2011). Is Secretion of Tumour-specific Antigen Important for Cancer Eradication by CD4+T Cells? - Implications for Cancer Immunotherapy by Adoptive T Cell Transfer. Scandinavian Journal of Immunology. ISSN 0300-9475. 73(6), p. 527–530. doi: 10.1111/j.1365-3083.2011.02558.x. Full text in Research Archive
• Funderud, Ane; Aas-Hanssen, Kristin; Aksaas, Anne Kristin; Hafte, Tolesa Tilahun; Corthay, Alexandre & Munthe, Ludvig Andre [Show all 8 contributors for this article] (2009). Isoform-specific regulation of immune cell reactivity by the catalytic subunit of protein kinase A (PKA). Cellular Signalling. ISSN 0898-6568. 21(2), p. 274–281. doi: 10.1016/j.cellsig.2008.10.013. Full text in Research Archive
• Corthay, Alexandre; Lundin, Katrin; Lorvik, Kristina Berg; Hofgaard, Peter Olaf & Bogen, Bjarne (2009). Secretion of Tumor-Specific Antigen by Myeloma Cells Is Required for Cancer Immunosurveillance by CD4(+) T Cells. Cancer Research. ISSN 0008-5472. 69(14), p. 5901–5907. doi: 10.1158/0008-5472.CAN-08-4816. Full text in Research Archive
• Corthay, Alexandre (2007). CD4+T cells cooperate with macrophages for specific elimination of MHC class II-negative cancer cells. Advances in Experimental Medicine and Biology. ISSN 0065-2598. 590, p. 195–208. Full text in Research Archive
• Bogen, Bjarne; Ruffini, Pier Adelchi; Corthay, Alexandre; Brunsvik, Agnete; Frøyland, Marianne & Lundin, Katrin [Show all 9 contributors for this article] (2006). Idiotype-specific immunotherapy in multiple myeloma: suggestions for future directions of research. Studies in Surface Science and Catalysis. ISSN 0167-2991. 91, p. 941–948. Full text in Research Archive
• Munthe, Ludvig Andre; Corthay, Alexandre; Os, Audun; Zangani, Michael M & Bogen, Bjarne (2005). Systemic autoimmune disease caused by autoreactive B cells that receive chronic help from immunoglobulin V region-specific T cells. Journal of Immunology. ISSN 0022-1767. 175, p. 2391–2400. Full text in Research Archive
• Corthay, Alexandre; Skovseth, Dag Kristian; Lundin, Katrin; Røsjø, Egil; Omholt, Hilde & Hofgaard, Peter Olaf [Show all 8 contributors for this article] (2005). Primary antitumor immune response mediated by CD4+ T cells. Immunity. ISSN 1074-7613. 22, p. 371–383. Full text in Research Archive
• Corthay, Alexandre; Lundin, Katrin; Munthe, Ludvig Andre; Frøyland, Marianne; Gedde-Dahl, Thobias & Dembic, Zlatko [Show all 7 contributors for this article] (2004). Immunotherapy in multiple myeloma: Id-specific strategies suggested by studies in animal models. Cancer Immunology and Immunotherapy. ISSN 0340-7004. 53, p. 759–769. Full text in Research Archive
• Tjelle, TE; Corthay, Alexandre; Lunde, Elin; Sandlie, Inger; Michaelsen, Terje Einar & Mathiesen, I [Show all 7 contributors for this article] (2004). Monoclonal antibodies produced by muscle after plasmid injection and electroporation. Molecular Therapy. ISSN 1525-0016. 9(3), p. 328–336. Full text in Research Archive

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• Loevenich, Simon; Hernandez-valenzuela, Sofia; Wågbø, Ane Marit; Eidsaa, Marius; Sletta, Kristine & Haslene-Hox, Hanne [Show all 10 contributors for this article] (2025). Morphological profiling of mammalian macrophages. Full text in Research Archive
• Anderson, Colin C.; Bonney, Elizabeth A.; Mueller, Thomas F.; Corthay, Alexandre Benoit; Havele, Calliopi & Singh, Nevil J. [Show all 8 contributors for this article] (2023). On antigen-specific signals, immune class regulation and energetics: Report III from the workshops on foundational concepts of immune regulation. Scandinavian Journal of Immunology. ISSN 0300-9475. 98(3). doi: 10.1111/sji.13311. Full text in Research Archive Show summary

  Abstract This is a report from a one‐week workshop held in Athens, Greece in July of 2022. The workshop aimed to identify emerging concepts relevant to the fundamentals of immune regulation and areas for future research. Theories of immune regulation emphasize the role of T cell help or co‐stimulation (signal 2). The workshop participants considered how new data on the characteristics of agonist antigens, the role of the antigen receptor signals (signal 1) in driving fate decisions, the effect of energetics on immunity and a better understanding of class‐control in the immune response, may impact theories of immune regulation. These ideas were discussed in the context of tumour immunology, autoimmunity, pregnancy and transplantation. Here we present the discussions as a narrative of different viewpoints to allow the reader to join the conversation. These discussions highlight the evolving understanding of the nature of specific antigen recognition and how both antigen‐specific and non‐specific mechanisms impact immune responses.

• Corthay, Alexandre & Höglund, Petter (2022). Immunology according to Dembic: Preserving integrity is key. Scandinavian Journal of Immunology. ISSN 0300-9475. 95(5). doi: 10.1111/sji.13173. Full text in Research Archive
• Wold, Christian Winther; Corthay, Alexandre; Wangensteen, Helle & Inngjerdingen, Kari Tvete (2020). Myteomspunnen kjuke frå folkemedisin til mogleg kreftbehandling. www.forskning.no. Full text in Research Archive
• Gilmour, Brian Christopher; Corthay, Alexandre Benoit & Øynebråten, Inger (2019). Optimising the activation of dendritic cells to promote anti-cancer T cell responses. Full text in Research Archive
• Corthay, Alexandre (2017). Book Review: The foundations of immunology and their pertinence to medicine. Scandinavian Journal of Immunology. ISSN 0300-9475. 86(2), p. 119–120. doi: 10.1111/sji.12565. Full text in Research Archive
• Corthay, Alexandre (2016). Book Review: Rediscovering the Immune System as an Integrated Organ. Scandinavian Journal of Immunology. ISSN 0300-9475. 84(1), p. 70–71. doi: 10.1111/sji.12440. Full text in Research Archive
• Haabeth, Ole Audun; Lorvik, Kristina Berg; Hammarström, Clara Louise; Donaldson, Ian M; Haraldsen, Guttorm & Bogen, Bjarne [Show all 7 contributors for this article] (2016). Kreft-spesifikke betennelsesreaksjoner kan beskytte mot kreft. Bestpractice Onkologi/Hematologi. ISSN 2245-0440. February. Full text in Research Archive
• Müller, Elisabeth; Stavna, A.; Jahnsen, Frode Lars; Bakke, Oddmund & Corthay, Alexandre (2013). Using Live Imaging to Investigate the Mechanisms Underlying Tumor Cell Killing by Macrophages. Scandinavian Journal of Immunology. ISSN 0300-9475. 77(4), p. 275–276. Full text in Research Archive
• Corthay, Alexandre; Hammarström, Clara; Fauskanger, M.; Haabeth, OAW; Zangani, Miriam & Haraldsen, H. [Show all 8 contributors for this article] (2012). Cancer immunotherapy by adoptive transfer of tumor-specific Th2 cells. Immunology. ISSN 0019-2805. 137, p. 706–706. Full text in Research Archive
• Lorvik, Kristina Berg; Bogen, Bjarne & Corthay, Alexandre (2012). Fingolimod blocks immunosurveillance of myeloma and B-cell lymphoma resulting in cancer development in mice. Blood. ISSN 0006-4971. 119(9), p. 2176–2177. doi: 10.1182/blood-2011-10-388892. Full text in Research Archive
• Haabeth, Ole Audun; Lorvik, Kristina Berg; Hammarstrom, C; Donaldson, Ian Matthew; Haraldsen, Guttorm & Bogen, Bjarne [Show all 7 contributors for this article] (2011). A cancer-protective role of inflammation. Cytokine. ISSN 1043-4666. 56(1), p. 101–101. doi: 10.1016/j.cyto.2011.07.392. Full text in Research Archive
• Haabeth, Ole Audun; Lorvik, Kristina Berg; Hammarström, Clara; Donaldson, Ian Matthew; Haraldsen, Guttorm & Bogen, Bjarne [Show all 7 contributors for this article] (2011). Cancer Immunosurveillance by CD4(+) T Cells. Scandinavian Journal of Immunology. ISSN 0300-9475. 73(6), p. 603–603. Full text in Research Archive
• Lorvik, Kristina Berg; Zangani, Michael Mehrdad; Bogen, Bjarne & Corthay, Alexandre (2011). Myeloma Immunotherapy by Adoptive Transfer of Idiotype-Specific Th2 Cells. Scandinavian Journal of Immunology. ISSN 0300-9475. 73(4), p. 392–392. Full text in Research Archive
• Alfsnes, Katrine; Lorvik, Kristina Berg; Audun, Ole; Haabeth, Werner; Bogen, Bjarne & Corthay, Alexandre (2011). Workshop IV - Tumor Immunology and Infectious Diseases Immunology. Scandinavian Journal of Immunology. ISSN 0300-9475. 73(4), p. 380–380. Full text in Research Archive
• Haabeth, Ole Audun; Lorvik, Kristina Berg; Hammarström, Clara; Donaldson, Ian Matthew; Haraldsen, Guttorm & Bogen, Bjarne [Show all 7 contributors for this article] (2011). Inflammation Driven by Tumor-Specific Th1 Cells Protects against B-Cell Cancer. Scandinavian Journal of Immunology. ISSN 0300-9475. 73(4), p. 384–384. Full text in Research Archive
• Haabeth, Ole Audun; Lorvik, Kristina Berg; Bogen, Bjarne & Corthay, Alexandre (2009). Cytokine profile of successful cancer immunosurveillance mediated by tumor-specific CD4(+) T cells. Cytokine. ISSN 1043-4666. 48(1-2), p. 48–48. doi: 10.1016/j.cyto.2009.07.135. Full text in Research Archive
• Corthay, Alexandre (2009). How do Regulatory T Cells Work? Scandinavian Journal of Immunology. ISSN 0300-9475. 70(4), p. 326–336. doi: 10.1111/j.1365-3083.2009.02308.x. Full text in Research Archive
• Haabeth, OAW; Lorvik, Kristina Berg; Aagaard, L; Bogen, Bjarne & Corthay, Alexandre (2008). Role of cytokines and chemokines for cancer immune prevention. Scandinavian Journal of Immunology. ISSN 0300-9475. 68, p. 218–218. Full text in Research Archive
• Lorvik, Kristina Berg; Corthay, Alexandre; Lundin, Katrin; Hofgaard, Peter Olaf; Omholt, Hilde & Bogen, Bjarne (2008). Role of antigen secretion for cancer immunosurveillance. Scandinavian Journal of Immunology. ISSN 0300-9475. 68, p. 217–218. Full text in Research Archive
• Corthay, Alexandre; Lorvik, Kristina Berg; Hofgaard, Peter Olaf; Omholt, Hilde & Bogen, Bjarne (2008). Transcriptomics of a successful antitumor immune response. Scandinavian Journal of Immunology. ISSN 0300-9475. 68, p. 209–209. Full text in Research Archive
• Corthay, Alexandre (2006). A three-cell model for activation of naive T helper cells. Scandinavian Journal of Immunology. ISSN 0300-9475. 64, p. 93–96. Full text in Research Archive
• Halstensen, Trond Sundby; Corthay, Alexandre & Westgaard, Arne (2005). Immunologiens dag 29. april 2005 - populærvitenskapelig konferanse i universitetets aula. [Internet]. Norsk Selskap for Immunologi - www.norwegianimmunology.org. Full text in Research Archive Show summary

  Den europeiske immunologiforeningen EFIS innstiftet "Day of Immunology", som ble markert for første gang den 29. april 2005. Norsk Selskap for Immunologi (NSI) var ansvarlig for arrangementene i Norge.

• Halstensen, Trond Sundby; Westgaard, Arne & Corthay, Alexandre (2005). NSI's Annual General Meeting 2005. [Internet]. Abstraktbok utgitt i papirform. Full text in Research Archive
• Corthay, Alexandre & Stankovic, Branislava (2015). Characterization of immune cells in human non-small cell lung cancer (Thesis for the Master’s Degree in Molecular Biosciences). Norges miljø- og biovitenskapelige universitet (NMBU). Full text in Research Archive
• Joly-Battaglini, A & Corthay, Alexandre (2015). Study of immune cells infiltrating human non-small cell lung cancer (Thesis for the Master’s Degree in Biology). Université Paris Sud. Full text in Research Archive

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