Peripheral ICOS+CD4 T cell frequency: An indicator for short-term progression in resectable advanced gastric cancer following platinum-based chemotherapy

Peripheral frequency of inducible T cell co-stimulator (ICOS) + CD4 T cells is associated with early response to immunotherapy and prognosis in gastric cancer (GC); however, limited studies have clarified its association with chemotherapy response. This was a prospective, pilot study. A total of 120 participants with newly diagnosed GC were recruited; 50 advanced GC patients (T3-4N1-3M0-1) underwent curative surgery followed by platinum-based chemotherapy, and their prognosis and survival were assessed. The frequency of ICOS + CD4 T cells in the peripheral blood of each patient was examined using flow cytometry. The frequency of ICOS+CD4 T cells in stage III GC patients was significantly higher than that of stages I and II combined (p = 0.0204) and stage IV GC patients (p = 0.0117). In xenograft GC animals, a positive correlation was noted between the peripheral frequency of ICOS + CD4 and the tumor volume in mice (p = 0.0496). Co-culture experiments showed that the presence of GC cells increased the ratio of ICOS + CD4 T cells derived from peripheral blood in a dose-dependent manner. The initial peripheral frequency of ICOS + CD4 T cells in the GC progression-group was significantly lower than that in the stable-group after 3 months of platinum-based chemotherapy (p = 0.0318). High frequency of peripheral ICOS + CD4 was significantly positively correlated with peripheral IFN-γ concentration in tumor-bearing mice. The frequency of ICOS + CD4 serves as an index reflecting the tumor burden of GC. It effectively predicts the short-term progression risk for resectable advanced GC under platinum-based chemotherapy, primarily because it can reflect the basal immune status of the body.