Deciphering the role of CD8+ tissue-resident memory T cells in anti-cancer immunity

• Applicant: Philippa Meiser
• Subject Area: Immunology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 556373788

Cancer is one of the leading causes of death worldwide, and although immunotherapeutic approaches harnessing the patients’ own immune cells for the treatment of tumors have shown some success, many patients do not respond to immunotherapy. CD8+ T cells play a crucial role during the anti-tumor immune response and are the target cells of many immunotherapeutic approaches; however, the CD8+ T cell population in the tumor microenvironment (TME) is heterogeneous and it is unclear how different CD8+ T cell subsets contribute to the success of immunotherapy. A CD8+ T cell subset that has been shown to be associated with increased patient survival and improved responsiveness to immunotherapy in multiple cancer types is CD8+ tissue-resident memory T cells (TRM). TRM are phenotypically and functionally distinct from other CD8+ T cell subsets, such as circulatory CD8+ memory T cells or effector CD8+ T cells. While the role of TRM as key cells during responses against secondary infections has been well established, their contribution to anti-cancer immunity remains incompletely understood. The proposed project therefore aims to reveal the mechanisms underlying TRM development and function in tumors. Analyses involving confocal microscopy and spatial transcriptomics of a murine breast cancer model as well as human breast cancer samples will be used to identify TRM-specific spatiotemporal dynamics and cellular neighborhoods in the TME. Interactions between TRM and other immune cells in the TME, such as dendritic cells and CD4+ T cells, will be defined and the functional consequences of a loss of these interactions will be investigated using transgenic mouse models. By uncovering the differences in the localization and interactions of intratumoral TRM compared to other CD8+ T cell subsets, the project will deepen the knowledge on how individual CD8+ T cell populations influence anti-cancer immunity. In this manner, a comprehensive map of intratumoral TRM niches in breast cancer will be established during the proposed project. Not only will the findings improve the understanding of how TRM promote cancer patient survival and responsiveness to immunotherapy, but they might also reveal novel targets for therapeutic approaches aiming to support TRM function during the anti-tumor immune response.

• DFG Programme: WBP Fellowship
• International Connection: Australia
• Host: Dr. Laura Mackay