With recent studies uncovering the complex landscape of immune checkpoint regulators in gastric cancer (GC), we aimed to characterize the expression of the checkpoint proteins V-domain Ig suppressor of T-cell activation (VISTA), programmed cell death 1 ligand 1 (PD-L1), and programmed cell death protein-1 (PD-1) in a cohort of GCs following platinum-based neoadjuvant chemotherapy. A total of 141 GC samples, 93 lymph node metastases, and 15 distant metastases were assessed using immunohistochemistry. Staining results were correlated with clinicopathological patient characteristics, genetic alterations, and survival. The expression of VISTA was detected in tumor cells of 38 (30.9%) GCs and immune cells of 139 (98.6%) GCs. The expression of PD-L1 was detected in tumor cells of 27 (22.7%) GCs and immune cells of 134 (96.4%) GCs. The expression of PD-1 was only observed in lymphocyte aggregates/intratumoral lymphoid follicles of 123 (87.2%) GCs. VISTA and PD-L1 correlated in their expression and were associated with poor tumor regression. Compared with an ancient cohort of therapy naïve GCs, we observed a major increase in overall immune cell density accompanied by an over proportional increase in PD-1 and VISTA-positive immune cells. The frequency of VISTA expression in tumor cells was also found to be substantially increased. To the contrary, expression of PD-L1 was decreased in immune cells and tumor cells of neoadjuvantly treated GCs. As a result, a subset of GCs using a single (only VISTA or PD-L1) or combined (VISTA and PD-L1) immune evasion mechanisms might benefit from an anti-PD-L1/anti-VISTA–targeted therapy.

最近的研究揭示了胃癌（GC）中免疫检查点调节剂的复杂情况，我们旨在表征T细胞活化（VISTA），程序性细胞死亡1配体1（PD）的检查点蛋白V域Ig抑制剂的表达-L1）和一组基于铂的新辅助化疗后的一组GC中的程序性细胞死亡蛋白1（PD-1）。使用免疫组织化学评估了总共141个GC样品，93个淋巴结转移和15个远处转移。染色结果与临床病理患者特征，遗传改变和生存率相关。在38个（30.9％）GC的肿瘤细胞和139个（98.6％）GC的免疫细胞中检测到VISTA的表达。在27个（22.7％）GC的肿瘤细胞和134个（96.4％）GC的免疫细胞中检测到PD-L1的表达。仅在123个（87.2％）GC的淋巴细胞聚集体/瘤内淋巴滤泡中观察到PD-1的表达。VISTA和PD-L1在它们的表达中相互关联，并且与不良的肿瘤消退有关。与古代未使用过GC的人群相比，我们观察到总体免疫细胞密度显着增加，而PD-1和VISTA阳性免疫细胞则呈比例增加。还发现肿瘤细胞中VISTA表达的频率显着增加。相反，PD-L1的表达在新辅助处理的GCs的免疫细胞和肿瘤细胞中降低。结果，使用单一（仅VISTA或PD-L1）或组合（VISTA和PD-L1）免疫逃逸机制的GC子集可能会受益于针对PD-L1 / anti-VISTA的靶向治疗。