Immunological impact of chemotherapy on the tumor microenvironment in gastric cancer
Qing Wei, Qi Xu, Yuan Xing, Jingjing Li, Lei Chen, Cong Luo, Xiu Zhu, Jie‐Er Ying
Abstract
Abstract Objective This study aimed to investigate alterations in pre‐ and post‐neoadjuvant chemotherapy (NACT) tumor‐infiltrating immune cells and subsequent evaluation of the predictive and prognostic value of these changes in gastric cancer (GC). Methods Fifty patients with GC underwent three cycles of S‐1 and oxaliplatin (SOX regimen)‐NACT. Paired samples from tumor lesions before and after NACT were available for all patients participating in the study. Immunohistochemistry was performed for T cell subsets (CD3 + and CD8 + ) and macrophages (CD68 + and CD163 + ). Results After NACT, the average expression levels of CD3, CD8, CD68, and CD163 were significantly increased ( p < .001 ). However, neither expression levels pre‐ nor post‐chemotherapy correlated with treatment response. Multivariate Cox regression analysis demonstrated that upregulation of CD8/CD3 levels (hazard ratio [HR] = 0.117; 95% confidence interval [CI] = 0.031–0.446; p = 0.002) and CD163 levels after chemotherapy (HR = 2.258; 95% CI = 1.047–4.867; p = 0.038) were independent prognostic factors of overall survival. Conclusion Chemotherapy in GC is useful to induce CD3 + and CD8 + T lymphocytes as well as CD68 + and CD163 + macrophages in the tumor microenvironment in combination with its direct cytotoxic effects. These results indicate that chemotherapy may play a role in tumor immune microenvironment remodeling.