Transcriptomic profiles of neoantigen-reactive T cells in human gastrointestinal cancers.
Publication Title
Cancer cell
Document Type
Article
Publication Date
4-11-2022
Keywords
oregon; portland; chiles; hood river; Antigens, Neoplasm; CD8-Positive T-Lymphocytes; Gastrointestinal Neoplasms; Humans; Lymphocytes, Tumor-Infiltrating; Transcriptome
Abstract
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.
Area of Special Interest
Digestive Health
Area of Special Interest
Cancer
Specialty/Research Institute
Gastroenterology
Specialty/Research Institute
Oncology
