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000285421 1001_ $$0P:(DE-He78)a7ebe54d5cb6cfa15c663da9ce1f9ab2$$aMeng, Zibo$$b0$$eFirst author$$udkfz
000285421 245__ $$aTranscriptome-based identification of tumor-reactive and bystander CD8+ T cell receptor clonotypes in human pancreatic cancer.
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000285421 520__ $$aPancreatic ductal adenocarcinoma (PDAC) is generally refractory to immune checkpoint blockade, although patients with genetically unstable tumors can show modest therapeutic benefit. We previously demonstrated the presence of tumor-reactive CD8+ T cells in PDAC samples. Here, we charted the tumor-infiltrating T cell repertoire in PDAC by combining single-cell transcriptomics with functional testing of T cell receptors (TCRs) for reactivity against autologous tumor cells. On the basis of a comprehensive dataset including 93 tumor-reactive and 65 bystander TCR clonotypes, we delineated a gene signature that effectively distinguishes between these T cell subsets in PDAC, as well as in other tumor indications. This revealed a high frequency of tumor-reactive TCR clonotypes in three genetically unstable samples. In contrast, the T cell repertoire in six genetically stable PDAC tumors was largely dominated by bystander T cells. Nevertheless, multiple tumor-reactive TCRs were successfully identified in each of these samples, thereby providing a perspective for personalized immunotherapy in this treatment-resistant indication.
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000285421 7001_ $$0P:(DE-He78)c083248353e32708b98dc20cb621c06a$$aRodriguez Ehrenfried, Aaron$$b1$$eFirst author$$udkfz
000285421 7001_ $$0P:(DE-He78)c78afd4e9332b1120bda149010bb3633$$aTan, Chin Leng$$b2$$eFirst author$$udkfz
000285421 7001_ $$0P:(DE-He78)fec6ef4ffbd92f019f904ba6809ec1b3$$aSteffens, Laura Katharina$$b3$$udkfz
000285421 7001_ $$0P:(DE-He78)37e53d333a7b0896397cbaa885b046b1$$aKehm, Hannes$$b4$$udkfz
000285421 7001_ $$0P:(DE-He78)17b0a821061db042fe4b6eff379d1ba6$$aZens, Stefan$$b5$$udkfz
000285421 7001_ $$0P:(DE-He78)67614eacdbe6fe4404a46d2f8d01ac52$$aLauenstein, Claudia$$b6$$udkfz
000285421 7001_ $$0P:(DE-He78)2b298456f6596fd1f3fbb23c521ccb62$$aPaul, Alina$$b7$$udkfz
000285421 7001_ $$0P:(DE-He78)41e96a40f6e5f7646b88ead1a776e077$$aSchwab, Marius$$b8$$udkfz
000285421 7001_ $$0P:(DE-He78)1dfe5fa05989d8b5eeb8bd098e2f1c1f$$aFörster, Jonas$$b9$$udkfz
000285421 7001_ $$0P:(DE-He78)154b320ef9a6e95f0081a85ef24eb3a3$$aSalek, Mogjiborahman$$b10
000285421 7001_ $$0P:(DE-He78)3743a1b712edca2ffa829b7096d7037e$$aRiemer, Angelika$$b11$$udkfz
000285421 7001_ $$aWu, Heshui$$b12
000285421 7001_ $$aEckert, Christoph$$b13
000285421 7001_ $$aLeonhardt, Carl-Stephan$$b14
000285421 7001_ $$aStrobel, Oliver$$b15
000285421 7001_ $$0P:(DE-He78)792fd96345efded9a78c902105479a68$$aVolkmar, Michael$$b16$$udkfz
000285421 7001_ $$0P:(DE-He78)e9c55f46b4b06cf835834ee7e3e00db8$$aPoschke, Isabel$$b17$$eLast author$$udkfz
000285421 7001_ $$0P:(DE-He78)81ae96953d6149e4307057d71a190019$$aOffringa, Rienk$$b18$$eLast author$$udkfz
000285421 773__ $$0PERI:(DE-600)2518839-2$$a10.1126/scitranslmed.adh9562$$gVol. 15, no. 722, p. eadh9562$$n722$$peadh9562$$tScience translational medicine$$v15$$x1946-6234$$y2023
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