Effect of Neoadjuvant Chemotherapy on Tumor-Infiltrating Lymphocytes in Resectable Gastric Cancer: Analysis from a Western Academic Center

Simple Summary In this investigation, we analyzed the number, type, and location of immune cells within surgically resected gastric cancer specimens treated with or without preoperative chemotherapy. We hypothesized that chemotherapy can stimulate the host immune system, as evidenced by an increased number of anti-tumor infiltrating lymphocytes in the tumor microenvironment. We found significantly elevated levels of immune cells within chemotherapy-treated tumors compared with chemotherapy-naive specimens. We also revealed important associations between survival and immune lymphocytes in the tumor-related stromal tissue. Together, we added evidence supporting the immunostimulatory role of chemotherapy and underscore the potential utility of immunotherapy in resectable gastric cancer.Abstract Tumor-infiltrating lymphocytes (TILs) are an emerging biomarker predictive of response to immunotherapy across a spectrum of solid organ malignancies. The characterization of TILs in gastric cancer (GC) treated with contemporary, multiagent neoadjuvant chemotherapy (NAC) is understudied. In this retrospective investigation, we analyzed the degree of infiltration, phenotype, and spatial distribution of TILs via immunohistochemistry within resected GC specimens treated with or without NAC at a Western center. We hypothesized that NAC executes immunostimulatory roles, as evidenced by an increased number of anti-tumor TILs in the tumor microenvironment. We found significantly elevated levels of conventional and memory CD8+ T cells, as well as total TILs (CD4+, CD8+, Treg, B cells), within chemotherapy-treated tumors compared with chemotherapy-naive specimens. We also revealed important associations between survival and pathologic responses with enhanced TIL infiltration. Taken together, our findings advocate for an immunostimulatory role of chemotherapy and underscore the potential synergistic effect of combining chemotherapy with immunotherapy in resectable gastric cancer.