Predictive response and outcome of peripheral CD4+ T cell subpopulations to combined immunotherapy and chemotherapy in advanced gastric cancer patients

The identification of predictive biomarkers for patient stratification in immunotherapy is of utmost importance, given the limited benefit observed in certain populations. However, only limited information is so far available on the association between peripheral CD4+ T cell subpopulations and immunotherapy for advanced gastric cancer. Our current report aimed to investigate the predictive value of peripheral CD4+ T cell subpopulations in advanced gastric cancer patients treated with immunotherapy.A retrospective cohort analysis of 169 advanced gastric cancer patients treated with sintilimab combined with capecitabine and oxaliplatin in The Affiliated Xinghua People's Hospital, Medical School of Yangzhou University (Xinghua, China) between June 2019 and October 2022 was conducted. Clinical outcomes of peripheral CD4+ T cell subpopulations were analyzed by receiver operating characteristic (ROC) curve, chi-square test, Kaplan-Meier method and the univariate and multivariate Cox proportional hazards regression models.The optimal cutoff values for percentages of CD4+ T cells, naive CD4+ T cells (CD4+ Tn), memory CD4+ T cells (CD4+ Tm), central memory CD4+ T cells (CD4+ Tcm) and effector memory CD4+ T cells (CD4+ Tem) expressing PD-1 were 30.16 %, 17.79 %, 42.49 %, 31.54 % and 74.64 %, respectively. It was found that the percentages of CD4+ T, CD4+ Tn, CD4+ Tm, CD4+ Tcm and CD4+ Tem expressing PD-1 were significantly higher in responder (R) than non-responder (NonR) advanced gastric cancer patients associated with a longer progression free survival (PFS) and overall survival (OS). This correlation was also observed in the PD-L1 combined positive score (CPS) ≥ 5 populations. Univariate and multivariate Cox regression analyses indicated that lower CD4+ T, CD4+ Tn, CD4+ Tm, CD4+ Tcm and CD4+ Tem expressing PD-1 were independent risk factors of PFS and OS in advanced gastric cancer patients treated with combined immunotherapy and chemotherapy.The peripheral CD4+ T cell subpopulations demonstrated the high predictive value for therapeutic response and prolonged survival outcomes in advanced gastric cancer patients. CD4+ T cell subpopulations have the potential in predicting and screening benefit populations in advanced gastric cancer patients.