A Four-Factor Immunoscore System That Predicts Clinical Outcome for Stage II/III Gastric Cancer

The American Joint Committee on Cancer (AJCC) staging system is insufficiently prognostic for operable gastric cancer patients; therefore, complementary factors are under intense investigation. Although the focus is on immune markers, the prognostic impact of a single immune factor is minimal, due to complex antitumor immune responses. A more comprehensive evaluation may engender more accurate predictions. We analyzed immune factors by immunohistochemical staining in two independent cohorts. The association with patients' survival was analyzed by the Kaplan-Meier method. Our immunoscore system was constructed using Cox proportional hazard analysis. PD-L1⁺ immune cells (IC), PD-L1⁺ tumor cells (TC), PD-1^hi, and CD8^More were found among 33.33%, 31.37%, 33.33%, and 49%, respectively, of patients from the discovery cohort, and 41.74%, 17.4%, 38.26%, and 30.43% from the validation cohort. PD-L1⁺ ICs and PD-1^hi ICs correlated with poorer overall survival (OS), but PD-L1⁺ TCs correlated with better OS and clinical outcomes and infiltration of more CD8⁺ T cells. These four factors were independently prognostic after tumor/lymph nodes/metastasis (TNM) stage adjustment. An immunoscore system based on hazard ratios of the four factors further separated gastric cancer patients with similar TNM staging into low-, medium-, or high-risk groups, with significantly different survival. Our prognostic model yielded an area under the receiver operating characteristic curve (AUC) of 0.856 for prediction of mortality at 5 years, superior to that of TNM staging (AUC of 0.676). Thus, this more comprehensive immunoscore system can provide more accurate prognoses and is an essential complement to the AJCC staging system for operable gastric cancer patients. Cancer Immunol Res; 5(7); 524-34. ©2017 AACR.