%0 Journal Article
%A Meng, Zibo
%A Rodriguez Ehrenfried, Aaron
%A Tan, Chin Leng
%A Steffens, Laura Katharina
%A Kehm, Hannes
%A Zens, Stefan
%A Lauenstein, Claudia
%A Paul, Alina
%A Schwab, Marius
%A Förster, Jonas
%A Salek, Mogjiborahman
%A Riemer, Angelika
%A Wu, Heshui
%A Eckert, Christoph
%A Leonhardt, Carl-Stephan
%A Strobel, Oliver
%A Volkmar, Michael
%A Poschke, Isabel
%A Offringa, Rienk
%T Transcriptome-based identification of tumor-reactive and bystander CD8+ T cell receptor clonotypes in human pancreatic cancer.
%J Science translational medicine
%V 15
%N 722
%@ 1946-6234
%C Washington, DC
%I AAAS
%M DKFZ-2023-02366
%P eadh9562
%D 2023
%Z #EA:D200#EA:D170#LA:D200#LA:D170# / HI-TRON
%X Pancreatic ductal adenocarcinoma (PDAC) is generally refractory to immune checkpoint blockade, although patients with genetically unstable tumors can show modest therapeutic benefit. We previously demonstrated the presence of tumor-reactive CD8+ T cells in PDAC samples. Here, we charted the tumor-infiltrating T cell repertoire in PDAC by combining single-cell transcriptomics with functional testing of T cell receptors (TCRs) for reactivity against autologous tumor cells. On the basis of a comprehensive dataset including 93 tumor-reactive and 65 bystander TCR clonotypes, we delineated a gene signature that effectively distinguishes between these T cell subsets in PDAC, as well as in other tumor indications. This revealed a high frequency of tumor-reactive TCR clonotypes in three genetically unstable samples. In contrast, the T cell repertoire in six genetically stable PDAC tumors was largely dominated by bystander T cells. Nevertheless, multiple tumor-reactive TCRs were successfully identified in each of these samples, thereby providing a perspective for personalized immunotherapy in this treatment-resistant indication.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:37967201
%R 10.1126/scitranslmed.adh9562
%U https://inrepo02.dkfz.de/record/285421