Due to copyright issues, an electronic copy of the thesis must be ordered from the faculty. For the faculty to have time to process the order, the order must be received by the faculty at the latest 2 days before the public defence. Orders received later than 2 days before the defence will not be processed. After the public defence, please address any inquiries regarding the thesis to the candidate.
Trial Lecture – time and place
See Trial Lecture.
Adjudication committee
- First opponent: Professor Kristoffer Hellstrand, Sahlgrenska University Hospital,
- Second opponent: Professor Therese Standal, NTNU - Norwegian University of Science and Technology,
- Third member and chair of the evaluation committee: Professor II Therese Sørlie, University of Oslo
Chair of the Defence
Professor II Guttorm Haraldsen, University of Oslo
Principal Supervisor
Anders Aune Tveita, University of Oslo
Summary
The ability of T cells to eliminate cancer cells, either directly or by orchestrating downstream anti-tumor immune responses, has made them a focal point in the search for new and improved immunotherapeutic treatment modalities. However, T cells have been shown to play a dual role in cancer, as they are involved in both carcinogenesis and tumor progression, especially in the context of hematological malignancies. Throughout this thesis, we studied the cellular interactions of different T cell subsets and their roles in both promoting and combating cancer.
We examined T:B cell interactions ex vivo in both healthy and malignant settings and showed that T helper (Th) cells influence B cell signaling by regulating CD45 phosphatase activity. While this process enhances normal immune function, it also supports the growth of malignant B cells in chronic lymphocytic leukemia. These findings offer new therapeutic opportunities to disrupt cancer-promoting interactions between Th and B cells.
We further evaluated the potential of chimeric antigen receptors (CARs) to manipulate T cell functions for improved cancer immunotherapy. Our studies on T helper cell interactions with macrophages demonstrated that CD4+ CAR T cells, targeted toward immunosuppressive macrophages, can be leveraged to reeducate them toward a tumor-killing and pro-inflammatory state. Additionally, we demonstrated that by using CAR-modified T cells, cytotoxic T cell responses can be expanded toward the tumor-associated carbohydrate antigen GM3(Neu5Gc), an antigen outside the scope of natural T cell recognition. Both CAR T cell approaches show therapeutic effects in various preclinical tumor models, with potential benefits for a large number of patients.
In summary, the thesis emphasizes the complex nature of T cell effector function in cancer and proposes new strategies for manipulating these responses.
Additional information
Contact the research support staff.