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Dissection of the T cell infiltrate in mouse pancreatic tumors reveals an extensive and diverse tumor-reactive T cell repertoire

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 pa...

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Autores principales: Kehm, Hannes Jakob (Autor) , Zens, Stefan (Autor) , Baumann, Daniel (Autor) , Meng, Zibo (Autor) , Ru, Arnoud H. de (Autor) , Tjokrodirijo, Rayman T. N. (Autor) , Vent, Caroline (Autor) , Murawjew, Olga (Autor) , Braun, Sarah (Autor) , Weiß, Anne (Autor) , Bieberich, Florian (Autor) , Daniel, Aline Sophie (Autor) , Lucato, Francesca (Autor) , Kühner, Janne (Autor) , Minguez, Sonia Gutierrez (Autor) , Tan, Chin Leng (Autor) , Förster, Jonas (Autor) , Salek, Mogjiborahman (Autor) , Riemer, Angelika (Autor) , Volkmar, Michael (Autor) , Veelen, Peter van (Autor) , Poschke, Isabel (Autor) , Offringa, Rienk (Autor)
Formato: Article (Journal)
Lenguaje:inglés
Publicado: 2026
In: Science advances
Year: 2026, Volumen: 12, Número: 15, Pages: 1-22
ISSN:2375-2548
DOI:10.1126/sciadv.adr6132
Acceso en línea:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1126/sciadv.adr6132
Verlag, lizenzpflichtig, Volltext: https://www.science.org/doi/10.1126/sciadv.adr6132
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Notas de Autor:Hannes Kehm, Stefan Zens, Daniel Baumann, Zibo Meng, Arnoud H. de Ru, Rayman T. N. Tjokrodirijo, Caroline Vent, Olga Murawjew, Sarah Braun, Anne Weiss, Florian Bieberich, Aline Konrad, Francesca Lucato, Janne Kühner, Sonia Gutierrez Minguez, Chin Leng Tan, Jonas D. Förster, Mogjiborahman Salek, Angelika B. Riemer, Michael Volkmar, Peter van Veelen, Isabel Poschke, Rienk Offringa
Descripción
Sumario: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.
Notas:Online veröffentlicht: 10. April 2026
Gesehen am 21.08.2026
Descripción Física:Online Resource
ISSN:2375-2548
DOI:10.1126/sciadv.adr6132

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