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- W4313406940 abstract "Abstract Granzymes are a class of cytotoxic proteases and are the primary mechanism utilized by T cells to directly eliminate cancer cells. Each granzyme acts upon a unique set of substrates in target cells to induce cytotoxicity through a range of different mechanisms. Granzymes are some of the most differentially regulated genes in CD8+ tumor infiltrating lymphocytes, relative to T cells outside of the tumor microenvironment (TME). We and others have determined by microarray and qPCR that granzyme F is highly upregulated in the TME. Granzyme F expression is restricted to a small subset of antigen-experienced and exhausted T cells, as determined by flow cytometry-based detection of granzyme F RNA transcripts and may represent a marker of a unique T cell cytotoxic function. Single cell RNA sequencing of CD8 TIL has revealed that granzyme F-high expressing cells are unique from both granzyme A and B expressing cells, and that it is therefore likely these TIL utilize a unique mechanism of cytotoxicity in their elimination of cancer cells. Recombinant granzyme F has previously been shown to induce a unique form of cell death, characterized as being caspase-independent and resulting in rupture of target cell plasma membrane. By over expressing granzyme F we are determining if this mechanism of cell death is leverageable to improve the cytotoxic capacity of TIL, and if induction of different forms of T cell-mediated cytotoxicity can modulate the immunogenicity of the TME. These experiments are designed to provide insight into how to improve adoptive T cell therapies by directly improving cytotoxicity, the terminal step of T cell interaction with tumor cells. This work was supported by the National Institutes of Health NIAID training grant (Training Program in Immunology; T32-AI07405) award to Zachary Hay" @default.
- W4313406940 created "2023-01-06" @default.
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- W4313406940 date "2022-05-01" @default.
- W4313406940 modified "2023-09-25" @default.
- W4313406940 title "Granzyme F production by CD8 T cells in the tumor microenvironment" @default.
- W4313406940 doi "https://doi.org/10.4049/jimmunol.208.supp.121.04" @default.
- W4313406940 hasPublicationYear "2022" @default.
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