Transcriptomic profiles of neoantigen-reactive T cells in human gastrointestinal cancers

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.

Automated summary

In this study, tumor-infiltrating lymphocytes from bile duct and pancreatic cancer patients were examined using immunological screening and single-cell RNA sequencing. The researchers found that neoantigen-reactive T cells infiltrating gastrointestinal cancers exhibited an exhausted state and had distinct transcriptomic signatures, which could potentially be utilized for therapy.