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

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. [Display omitted] •The expression of GITR varies greatly across T cell subsets and tissue types•GITR+ CD4 T cells contribute to the immunosuppressive microenvironment in human gastric cancer•GITR+ CD4 T cells correlate with worse prognosis in gastric cancer patients•GITR protein is mainly distributed intracellularly in PBMC-derived Treg cells Immunology; Cell biology; Cancer