Transcriptomic profiles of neoantigen-reactive T cells in human gastrointestinal cancers
C Zheng, JN Fass, YP Shih, AJ Gunderson, NS Silva… - Cancer Cell, 2022 - cell.com
C Zheng, JN Fass, YP Shih, AJ Gunderson, NS Silva, H Huang, BM Bernard…
Cancer Cell, 2022•cell.comTumor-infiltrating neoantigen-reactive T cells can mediate regression of metastatic
gastrointestinal cancers yet remain poorly characterized. We performed immunological
screening against personalized neoantigens in combination with single-cell RNA
sequencing on tumor-infiltrating lymphocytes from bile duct and pancreatic cancer patients
to characterize the transcriptomic landscape of neoantigen-reactive T cells. We found that
most neoantigen-reactive CD8+ T cells displayed an exhausted state with significant …
gastrointestinal cancers yet remain poorly characterized. We performed immunological
screening against personalized neoantigens in combination with single-cell RNA
sequencing on tumor-infiltrating lymphocytes from bile duct and pancreatic cancer patients
to characterize the transcriptomic landscape of neoantigen-reactive T cells. We found that
most neoantigen-reactive CD8+ T cells displayed an exhausted state with significant …
Summary
Tumor-infiltrating neoantigen-reactive T cells can mediate regression of metastatic gastrointestinal cancers yet remain poorly characterized. We performed immunological screening against personalized neoantigens in combination with single-cell RNA sequencing on tumor-infiltrating lymphocytes from bile duct and pancreatic cancer patients to characterize the transcriptomic landscape of neoantigen-reactive T cells. We found that most neoantigen-reactive CD8+ T cells displayed an exhausted state with significant CXCL13 and GZMA co-expression compared with non-neoantigen-reactive bystander cells. Most neoantigen-reactive CD4+ T cells from a patient with bile duct cancer also exhibited an exhausted phenotype but with overexpression of HOPX or ADGRG1 while lacking IL7R expression. Thus, neoantigen-reactive T cells infiltrating gastrointestinal cancers harbor distinct transcriptomic signatures, which may provide new opportunities for harnessing these cells for therapy.
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