Impact of PD-L1 high expression on the prognosis of patients with locally advanced gastric cancer.

e16103 Background: To investigate the relationship between PD-L1 expression and survival outcomes in patients (pts) with locally advanced gastric or gastroesophageal junction cancer (G/GEJC). Methods: Between December 2018 and November 2021, a cohort of pts who were confirmed pathological stage(pStage) II and III after D2 gastrectomy, were enrolled. None of the participants underwent neoadjuvant therapy, and postoperative tumor tissues were collected to evaluate PD-L1 expression. PD-L1 positive group was defined as CPS ≥ 1, while PD-L1 high expression group was defined as CPS ≥ 5. The impact of PD-L1 expression on pts survival was analyzed. Four PD-L1 positive pts from each of pStage II and III (a total of 8 cases) were randomly selected to analyze the tumor immune microenvironment (TIME) by multiplex immunofluorescence. Results: A total of 388 pts with locally advanced G/GEJC were enrolled, including 159 pts with pStage II and 229 with pStage III. Among these pStage III pts, 99 (43.2%), 84 (36.7%), and 46 (20.1%) were classified as pStage IIIA, IIIB, and IIIC, respectively. Of the total cohort, 262 (67.5%) pts were categorized as PD-L1 positive and 201 (51.8%) had PD-L1 high expression. The median follow-up period was 38 months (IQR: 28-48 months), with the final follow-up on June 30, 2023. In pStage II G/GEJC, no substantial differences were observed in 3-year disease-free survival (3y-DFS) (88.5% vs 87.9%, p = 0.939) or 3-year overall survival (3y-OS) (92.3% vs 89.9%, p = 0.621) between the PD-L1 positive and negative groups. Similarly, comparisons between PD-L1 high and low expression groups in pStage II pts revealed no significant variations in 3y-DFS (91.8% vs 84.2%, p = 0.138) or 3y-OS (94.2% vs 88.4%, p = 0.233). In contrast, among pStage III G/GEJC, PD-L1 positive pts had significantly inferior 3y-DFS (52.2% vs 67.8%, p = 0.030) and 3y-OS (65.1% vs 78.2%, p = 0.007) compared to PD-L1 negative pts. Likewise, 3y-DFS (50.2% vs 64.8%, p = 0.023) and 3y-OS (64.0% vs 75.1%, p = 0.036) were significantly better in the PD-L1 low expression group than in the high expression group. PD-L1 positive or high expression groups were not associated with TNM stage, HER-2 expression, MMR status, or EBV status. Multivariate analysis revealed that PD-L1 high expression was independently associated with shorter DFS (HR = 1.624, 95% CI: 1.056-2.500, p = 0.027) and OS (HR = 1.653, 95% CI: 1.016-2.688, p = 0.043) in pStage III G/GEJC pts. Preliminary analysis of the TIME showed that CD8+ T cells were mainly localized to the stroma in pStage II pts, whereas CD8+ T cells were mainly enriched in the tumor area of pStage III pts. Furthermore, PD-1+ cells were more abundant in pStage II pts compared to those in pStage III. Conclusions: PD-L1 high expression was associated with worse survival outcomes in pStage III G/GEJC pts and represented an independent adverse prognostic factor for DFS and OS.