Prognostic Significance of Categorizing Gastric Carcinoma by PD-L1 Expression and Tumor Infiltrating Lymphocytes

Goals. We categorized gastric cancers into four types of tumor immune microenvironment based on PD-L1 expression and tumor-infiltrating lymphocytes (TILs) to analyze clinicopathologic characteristics and recommend an immunotherapy-targetable subgroup. Procedures. Formalin-fixed, paraffin-embedded tissue samples of randomly selected gastric adenocarcinoma (n=479) were obtained and arrayed using a tissue-arraying instrument. Immunohistochemical stains for PD-L1, PD-1, and CD8 were performed and evaluated in addition to microsatellite instability, EBV infection, and HER-2 analyses. Results. Tumor microenvironment immune type (TMIT) I (both PD-L1-positive tumor cells & CD8-high TILs) and type III (PD-L1-positive tumor cells & CD8-low TILs) showed the best and worse prognosis, respectively. PD-L1 expression was significantly associated with Epstein-Barr virus infection (p<0.001) and microsatellite instability status (p<0.001). PD-L1 immunoreactivity was positively correlated with TILs having CD8 or PD-1 overexpression. Conclusions. TMIT I subgroup showed more patent CD8/PD-L1/PD-1 signaling pathway compared to other types. Therefore, TMIT I subgroup is a good candidate to predict effective response rate for immune checkpoint blockers. Such stratification of gastric cancers into four types can be used to predict the prognosis of patients and determine the immunotherapy-targetable subgroup.