Prognostic Impact of Immunoscore in Pathological Stage III Differentiated Gastric Cancer: A Multicenter Cohort Study Including PD-L1/PD-L2 Expression Analysis.

Background: The clinical use of the tumor microenvironment as a biomarker remains difficult in gastric cancer (GC). This multicenter, retrospective cohort study assessed the prognostic ability of the Immunoscore (IS) and the expression of programmed death ligand 1 (PD-L1) or programmed death ligand 2 (PD-L2) to select GC patients at higher risk of recurrence who may therefore require more intensive perioperative treatment. Methods: In 184 untreated pStage III GC patients who underwent radical gastrectomy at 13 institutions, IS (CD3+ and CD8+ lymphocytes) and PD-L1/2 expression were analyzed by immunohistochemistry using digital pathology HALO software. The associations between clinicopathological factors and prognosis were assessed. Results: Neither IS nor PD-L1/2 expression was a prognostic factor in the overall cohort. Subgroup analysis by histological type showed that in patients with differentiated-type GC, the high IS group had significantly better recurrence-free survival (RFS) (hazard ratio, 0.39; 95% confidence interval, 0.19-0.78; log-rank Conclusions: Histological classification may be useful in assessing the tumor microenvironment in GC, and patients with differentiated-type pStage III with a low IS signature may be candidates for more intensive perioperative treatment due to their higher risk of recurrence.