Elise Solli

• Solli, Elise; Bevilacqua, Alessio; Wenes, Mathias; Migliorini, Denis; Veen, Lars van der & Skånland, Sigrid [Vis alle 8 forfattere av denne artikkelen] (2026). The PI3Kδ inhibitor roginolisib (IOA-244) preserves T-cell function and activity. Molecular Oncology. ISSN 1574-7891. doi: 10.1002/1878-0261.70203. Fulltekst i vitenarkiv
• Wei, Qian; Hajjar, Ehsan; Cornillot‐Clément, Selma; Solli, Elise; Diaz, Nuria Garcia & Landskron, Johannes [Vis alle 9 forfattere av denne artikkelen] (2026). High-Throughput Phenotypic Screen to Identify FoxP3 Regulators in Primary T Cells. ACS Chemical Biology. ISSN 1554-8929. 21(4), s. 764–778. doi: 10.1021/acschembio.5c01019. Fulltekst i vitenarkiv Vis sammendrag

  FoxP3+ regulatory T cells (Tregs) maintain immune homeostasis by suppressing excessive antiself-immunity of effector T cells (Teffs) and thereby regulate autoimmunity and inhibit antitumor immune responses. Thus, Treg-targeting is a popular therapeutic strategy for both autoimmune diseases and cancer treatment. However, specific regulators of Tregs are needed to bypass adverse effects elicited by strategies that target molecules with overlapping expression between Tregs and other T cell subsets. We aim to identify small molecules that specifically target the key Treg lineage-defining transcription factor FoxP3. Here, we describe a high-throughput, flow-cytometry-based phenotypic screening assay, its data processing pipeline, and downstream methods for compound validation. We developed a set of algorithms to easily exclude compounds with high toxicity and to filter out autofluorescent compounds. Our screening assay is performed on human primary T cells by measuring FoxP3 levels in CD4+ T cells, using an automated liquid handling pipeline. Selected hit candidates from the screening were validated and assessed through functional analyses. From screening a library of approved drugs, we identified several candidates that regulate Treg functions through FoxP3. Seventeen chemical analogs of one hit compound were identified and characterized in cell-based assays, revealing structure–activity relationships and identifying compounds with more potent effects on the regulation of FoxP3 levels and Treg function. We conclude that this novel screening method could successfully identify FoxP3 regulators with an effect on Treg functions.

• Diaz, Nuria Garcia; Solli, Elise; Hajjar, Ehsan; Cornillot‐Clément, Selma; Landskron, Johannes & Ahmad, Rafi [Vis alle 8 forfattere av denne artikkelen] (2025). MAPK and STAT3 Inhibitors Modulate FoxP3 Expression and Regulatory T Cell Function. European Journal of Immunology. ISSN 0014-2980. 55(2). doi: 10.1002/eji.202451225. Fulltekst i vitenarkiv Vis sammendrag

  Regulatory T cells (Tregs) are a subset of T cells defined by the expression of Forkhead box protein P3 (FoxP3) playing a crucial role in regulating effector T cell activity. Tregs accumulate in the tumor microenvironment facilitating tumor growth. Thus, targeting FoxP3+ Tregs could improve cancer immunotherapies. Here, we conducted a high-throughput, phenotypic screening of a drug repurposing library to identify compounds downregulating FoxP3 expression in human primary T cells. We identified the tyrosine kinase inhibitor bosutinib and the STAT3 inhibitor nifuroxazide effectively downregulating FoxP3 expression. To identify more potent compounds, structural analogs of these two compounds were searched and validated. These analogs were found to reduce FoxP3 expression in a similar- or more potent manner than the original hits. All compounds inhibited Treg suppressive functions and reduced the expression of Treg activation markers. Importantly, bosutinib disrupted FAK and CaMKII signaling more potently in Tregs, whilst nifuroxazide and its analog NA16 targeted STAT3 protein levels more effectively in Tregs. Additionally, bosutinib and NA16 targeted effector Tregs more effectively than other Treg subsets. In summary, bosutinib, nifuroxazide, and their analogs inhibited FoxP3 expression, Treg suppressive abilities, and Treg activation effectively, which could serve as tools for the improvement of current cancer immunotherapies.

• Brynjulvsen, Marit; Solli, Elise; Walewska, Maria; Zucknick, Manuela; Djirackor, Luna & Langmoen, Iver Arne [Vis alle 10 forfattere av denne artikkelen] (2023). Functional and Molecular Heterogeneity in Glioma Stem Cells Derived from Multiregional Sampling. Cancers. 15(24). doi: 10.3390/cancers15245826. Fulltekst i vitenarkiv Vis sammendrag

  Glioblastoma (GBM) is an aggressive and highly heterogeneous primary brain tumor. Glioma stem cells represent a subpopulation of tumor cells with stem cell traits that are presumed to be the cause of tumor relapse. There exists complex tumor heterogeneity in drug sensitivity patterns between glioma stem cell (GSC) cultures derived from different patients. Here, we describe that heterogeneity also exists between GSC cultures derived from multiple biopsies within a single tumor. From biopsies harvested within spatially distinct regions representing the entire tumor mass, we established seven GSC cultures and compared their stem cell properties, mutations, gene expression profiles, and drug sensitivity patterns against 115 different anticancer drugs. The results were compared to 14 GSC cultures derived from other patients. Between the multiregional-derived GSC cultures, we observed only minor differences in their phenotype, proliferative capacity, and global gene expression. Further, they displayed intratumoral heterogeneity in mutational profiles and sensitivity patterns to anticancer drugs. This heterogeneity, however, did not exceed the extensive heterogeneity found between GSC cultures derived from other GBM patients. Our results suggest that the use of GSC cultures from one single focal biopsy may underestimate the overall complexity of the GSC population and display the importance of including GSC cultures reflecting the entire tumor mass in drug screening strategies.

Se alle arbeider i NVA

• Solli, Elise (2026). Enhancing tumor immunity by regulating T-cell tolerance. Universitetet i Oslo. ISSN 9788234808548. Fulltekst i vitenarkiv Vis sammendrag

  Cancer cells have developed sophisticated strategies to evade immune-mediated destruction. Tumor cells suppress immune activity through multiple mechanisms, including the upregulation of inhibitory ligands, recruitment of immunosuppressive cell populations, and secretion of suppressive cytokines or tumor-derived soluble factors. Although these inhibitory mechanisms serve a role in maintaining immune tolerance in healthy tissues, cancer cells co-opt them to their advantage. Selectively targeting these pathways therefore represents a critical opportunity to improve current cancer therapies. In this thesis, we investigated multifaceted approaches to enhance anti-tumor immunity by modulating T-cell activity and tolerance. Our work included a search for inhibitors of suppressive regulatory T cells (Tregs), the characterization of a novel PI3Kδ inhibitor, roginolisib, with respect to its effects on Treg and T-cell activity in the context of cancer treatment, and the elucidation of suppressive mechanisms mediated by programmed death-ligand 1 (PD-L1). First, we employed a high-throughput phenotypic screen to identify compounds capable of downregulating FoxP3 expression. This approach yielded two compounds, along with structural analogs, that effectively suppressed FoxP3 expression and impaired Treg suppressive function by targeting of the MAPK and STAT3 signaling pathways. Second, we demonstrated that roginolisib more effectively preserved T-cell proliferation and cytotoxic function, while inducing less activation of pro-inflammatory CD4+ T helper cells, compared to the widely used PI3Kδ inhibitor idelalisib. Notably, roginolisib retained comparable efficacy to idelalisib in inhibiting chronic lymphocytic leukemia (CLL) cell viability and downstream cell signaling. Finally, we made the unexpected observation that PD-L1 exerts both stimulatory and suppressive effects on healthy donor T cells through PD-1-independent mechanisms. Using AlphaFold Multimer, we identified 14 putative novel binding partners of PD-L1. While further investigation is warranted, antibody-mediated blockade of select candidate binding partners was found to modulate PD-L1-mediated effects on T cells. Overall, this thesis presents a broad exploration of strategies to enhance anti-tumor immunity and underscores the therapeutic potential of targeting T-cell tolerance mechanisms for the further development of cancer immunotherapies.

Se alle arbeider i NVA