CD8⁺ T cell subsets in acute infection and anti-tumor immunity

<p dir="ltr">CD8⁺ T cells are key immunotherapeutic targets due to their adaptability and functional diversity. This thesis investigates the utility of the chemokine receptor CX3CR1 in delineating CD8⁺ T cell functional potentials across various immunological contexts.</p><p dir="ltr">In paper I, we introduce the CX3CR1 expression gradient as a predictive tool for assessing the functional potential of memory CD8⁺ T cells in both human and mouse models. Paper II explores differentiation-unrelated factors influencing CX3CR1 levels in CD8⁺ T cell cultures. We, therefore, could propose better practices to expand CX3CR1 gradient utility to adoptive cell therapy applications. Paper III examines the phenotypic characteristics of CX3CR1+ CD8⁺ T cells that arise in response to tumour antigens. I propose that unidentified spatial factors influence anti-tumour CX3CR1+ CD8⁺ T cell functional potentials and drive intratumoral cells toward dysfunction. Together, these studies contribute to a deeper understanding of CX3CR1 as a biomarker for CD8⁺ T cell differentiation, offering insights to enhance the clinical outcomes of CD8⁺ T cell- based therapies.</p><h3>List of scientific papers</h3><p dir="ltr">I. Graded expression of the chemokine receptor CX3CR1 marks differentiation states of human and murine T cells and enables cross-species interpretation. Anthonie Johan Zwijnenburg, Jyoti Pokharel, Renata Varnaitė, Wenning Zheng, Elena Hoffer, IMAN SHRYKI, Natalia Ramirez Comet, Marcus Ehrstrom, Sara Gredmark-Russ, Liv Eidsmo, Carmen Gerlach. Immunity. 2023, 56(8), 1955-1974.e10. <a href="https://doi.org/10.1016/j.immuni.2023.06.025" rel="noreferrer" target="_blank">https://doi.org/10.1016/j.immuni.2023.06.025</a></p><p dir="ltr">II. The cellular microenvironment regulates CX3CR1 expression on CD8+ T cells and the maintenance of CX3CR1+ CD8+ T cells. Jyoti Pokharel*, IMAN SHRYKI*, Anthonie Johan Zwijnenburg, Ioana Sandu, Laura Krumm, Christina Bekiari, Rebecka Heinbäck, Victor Avramov, Josefin Lysell, Liv Eidsmo, Helena Erlandsson Harris and Carmen Gerlach. European Journal of Immunology. 2024, 54(1):e2350658. <a href="https://doi.org/10.1002/eji.202350658" rel="noreferrer" target="_blank">https://doi.org/10.1002/eji.202350658</a></p><p dir="ltr">III. CD8+ T cell responses to cytoplasmic antigens in anti-tumor immunity. IMAN SHRYKI, Natalia Ramirez Comet, Carmen Gerlach. [Manuscript]</p><p dir="ltr">* Equal contribution</p>