iScience (Dec 2022)

High-level of intratumoral GITR+ CD4 T cells associate with poor prognosis in gastric cancer

  • Shouyu Ke,
  • Feng Xie,
  • Yixian Guo,
  • Jieqiong Chen,
  • Zeyu Wang,
  • Yimeng Yu,
  • Haigang Geng,
  • Danhua Xu,
  • Xu Liu,
  • Xiang Xia,
  • Fengrong Yu,
  • Chunchao Zhu,
  • Zizhen Zhang,
  • Gang Zhao,
  • Bin Li,
  • Wenyi Zhao

Journal volume & issue
Vol. 25, no. 12
p. 105529

Abstract

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Summary: Immunotherapy targeting glucocorticoid-induced TNFR-related protein (GITR) exhibited strong anti-tumor capacity in mouse model but poor efficacy in clinical trials. This may be attributed to the different GITR expression mode between human and mouse. In this study, we analyzed single-cell RNA sequencing (scRNA-seq) data of human gastric cancer (GC) and used flow to explore the GITR expression across T cell subsets and tissue types in GC patients. We revealed that GITR+ CD4 T cells, including regulatory CD4 T (Treg) cells and conventional CD4 T (Tconv) cells, might contribute to the immunosuppressive microenvironment in GC. The enrichment of these cells was associated with a worse prognosis. Moreover, we found the cellular distribution of GITR protein in Treg cells was microenvironment dependent. In conclusion, GITR is still an important immune checkpoint need to be studied.

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