TY  - JOUR
AU  - Meng, Zibo
AU  - Rodriguez Ehrenfried, Aaron
AU  - Tan, Chin Leng
AU  - Steffens, Laura Katharina
AU  - Kehm, Hannes
AU  - Zens, Stefan
AU  - Lauenstein, Claudia
AU  - Paul, Alina
AU  - Schwab, Marius
AU  - Förster, Jonas
AU  - Salek, Mogjiborahman
AU  - Riemer, Angelika
AU  - Wu, Heshui
AU  - Eckert, Christoph
AU  - Leonhardt, Carl-Stephan
AU  - Strobel, Oliver
AU  - Volkmar, Michael
AU  - Poschke, Isabel
AU  - Offringa, Rienk
TI  - Transcriptome-based identification of tumor-reactive and bystander CD8+ T cell receptor clonotypes in human pancreatic cancer.
JO  - Science translational medicine
VL  - 15
IS  - 722
SN  - 1946-6234
CY  - Washington, DC
PB  - AAAS
M1  - DKFZ-2023-02366
SP  - eadh9562
PY  - 2023
N1  - #EA:D200#EA:D170#LA:D200#LA:D170# / HI-TRON
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:37967201
DO  - DOI:10.1126/scitranslmed.adh9562
UR  - https://inrepo02.dkfz.de/record/285421
ER  -