Transcriptomic profiles of neoantigen-reactive T cells in human gastrointestinal cancers.
oregon; portland; chiles; hood river; Antigens, Neoplasm; CD8-Positive T-Lymphocytes; Gastrointestinal Neoplasms; Humans; Lymphocytes, Tumor-Infiltrating; Transcriptome
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.
Zheng, Chunhong; Fass, Joseph N; Shih, Yi-Ping; Gunderson, Andrew J; Sanjuan Silva, Nelson; Huang, Huayu; Bernard, Brady M; Rajamanickam, Venkatesh; Slagel, Joseph; Bifulco, Carlo B; Piening, Brian; Newell, Pippa H A; Hansen, Paul D; and Tran, Eric, "Transcriptomic profiles of neoantigen-reactive T cells in human gastrointestinal cancers." (2022). Articles, Abstracts, and Reports. 6001.