Project Details
Projekt
The role of PGE2 production by ferroptotic cancer cells for regulation of anti-cancer T cell immunity
Applicant
Dr. Jan Philipp Böttcher
Subject Area
Cell Biology
Term
since 2021
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 461704785
Stem-like TCF1+CD8+ T cells drive immune responses to cancer. This unique role relies on the ability of stem-like TCF1+CD8+ T cells to give rise to anti-cancer effector CD8+ T cells through clonal expansion and effector differentiation within tumor tissue. Our previous work suggests that this process is regulated by cancer cells undergoing ferroptotic cell death, through mechanisms that remain to be investigated. Furthermore, the immunological consequences resulting from the interplay between stem-like CD8+ T cells and ferroptotic tumor cells have not been investigated so far. We aim to address these unresolved issues in this interdisciplinary proposal. We will investigate how ferroptotoic cells shape the immunological properties of anti-cancer stem-like CD8+ T cells and control their proliferative responses in tumors. Furthermore, we will address the consequences of cancer cell ferroptosis for T cell-mediated anti-cancer immunity, with a focus on the expansion and effector differentiation of tumor-infiltrating stem-like CD8+ T cells and their ability to mount protective responses within tumor tissue. Our preliminary experiments suggest that ferroptotic cells release immunosuppressive mediators that enable evasion of T cell-mediated anti-cancer immunity. Thus, a central aspect of our proposal is to elucidate how the release of such immunosuppressive mediators by ferroptotic cells affects T cell immunity driven by stem-like T cells in tumors, and whether this mechanism can be targeted therapeutically to enable cancer immune control. Our proposal will give novel insights into the immunological consequences of ferroptosis in cancer and its impact on anti-cancer immunity. We anticipate that understanding these processes will help the development of novel approaches for cancer patient treatment.
DFG Programme
Priority Programmes
