The T-Cell-Inflammation Status Can Predict Outcomes of Adjuvant Chemotherapy in Patients with Gastric Cancer.

Background: Immunogenic chemotherapy promotes antitumor immune response in the tumor microenvironment (TME). In gastric cancer, the effect of a preexisting T-cell-inflamed TME on the efficacy of adjuvant chemotherapy (ACT) is unclear. The purpose of the present study was to evaluate the benefits of ACT in T-cell-inflamed gastric cancer.

Methods: Three cohorts (n = 267, 300, and 198) of gastric cancer patients who underwent gastrectomy with or without ACT were included in this study. Based on a well-defined T-cell-inflamed gene signature, which includes 13 genes, these patients were classified into non-T-cell-inflamed, intermediate T-cell-inflamed, and T-cell-inflamed subgroups. The CIBERSORT software was used to estimate the immune cells infiltrating the TME, and the Kaplan-Meier curve was plotted for survival analysis.

Results: The T-cell-inflamed patients had high levels of CD8 + T, gamma delta T, and activated CD4 + memory T cells, whereas low level of resting NK cells was observed in all the three cohorts (all P < 0.05). In patients with stage II-IV disease without distant metastasis, those who were T-cell-inflamed were more likely to benefit from ACT (all P < 0.05), regardless of the chemotherapy regimen. Furthermore, patients with both T-cell-inflamed and high microsatellite instability status also were likely to benefit from ACT (P = 0.019).

Conclusions: The present study shows that T-cell inflammation is predictive of a survival benefit from ACT. Our findings will be helpful in making decisions regarding the use of chemotherapy in combination with immunotherapy to improve the clinical outcomes in patients with gastric cancer.