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| Home > Publications database > Dissection of the T cell infiltrate in mouse pancreatic tumors reveals an extensive and diverse tumor-reactive T cell repertoire. |
| Journal Article | DKFZ-2026-00847 |
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2026
Assoc.
Washington, DC [u.a.]
Abstract: Although pancreatic cancer is generally refractory to immune checkpoint blockade, recent studies of tumor-infiltrating T cells in human tumor samples demonstrated the presence of in vivo expanded, tumor-reactive T cell receptor (TCR) clonotypes. Here, we explored the T cell repertoire in a murine pancreatic cancer model by combining single-cell transcriptomics with functional TCR characterization. This uncovered a substantial diversity of tumor-reactive TCR clonotypes. Whereas some of these were exclusively reactive against the autologous tumor, most TCRs reacted against syngeneic tumor cells of diverse tissue origin. Immunopeptidome analyses revealed three T cell epitopes reflecting distinct tumor antigen classes also found in human cancers: a mutanome-encoded neoantigen, an epitope encoded by an ectopically expressed endogenous retroviral provirus, and an epitope derived from a cell stress-induced autoantigen. These findings underline the importance of uncovering the antigen specificity of the natural tumor-reactive TCR repertoire to assess its therapeutic potential and safety with regard to personalized immunotherapy.
Keyword(s): Animals (MeSH) ; Pancreatic Neoplasms: immunology (MeSH) ; Pancreatic Neoplasms: pathology (MeSH) ; Pancreatic Neoplasms: genetics (MeSH) ; Pancreatic Neoplasms: metabolism (MeSH) ; Mice (MeSH) ; Receptors, Antigen, T-Cell: immunology (MeSH) ; Receptors, Antigen, T-Cell: genetics (MeSH) ; Receptors, Antigen, T-Cell: metabolism (MeSH) ; Lymphocytes, Tumor-Infiltrating: immunology (MeSH) ; Lymphocytes, Tumor-Infiltrating: metabolism (MeSH) ; T-Lymphocytes: immunology (MeSH) ; T-Lymphocytes: metabolism (MeSH) ; Humans (MeSH) ; Epitopes, T-Lymphocyte: immunology (MeSH) ; Epitopes, T-Lymphocyte: genetics (MeSH) ; Antigens, Neoplasm: immunology (MeSH) ; Disease Models, Animal (MeSH) ; Single-Cell Analysis (MeSH) ; Cell Line, Tumor (MeSH) ; Receptors, Antigen, T-Cell ; Epitopes, T-Lymphocyte ; Antigens, Neoplasm
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