Details

Autor(en) / Beteiligte

• 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.
• Tran, Eric

Titel

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

Ist Teil von

• Cancer cell, 2022-04, Vol.40 (4), p.410-423.e7

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2022

Quelle

Access via ScienceDirect (Elsevier)

Beschreibungen/Notizen

• 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. [Display omitted] •scRNA-seq and in vitro screening methods identify bonafide neoantigen-reactive TIL•Most CD8+ and CD4+ neoantigen-reactive TIL display an exhausted state•CD8+ neoantigen-reactive TIL are enriched in CXCL13 and GZMA co-expression•CD4+ neoantigen-reactive TIL are enriched in HOPX or ADGRG1 expression Zheng et al. use single-cell RNA-seq with in vitro immunological screening assays to identify and characterize neoantigen-reactive T cells infiltrating cholangiocarcinoma and pancreatic cancer. They find that most CD8+ and CD4+ neoantigen-reactive T cells harbor an exhaustion signature with distinct transcriptomic profiles, thereby providing biological insight into this class of therapeutically relevant cells.