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Therapy Resistance in Neoadjuvantly Treated Gastric Cancer and Cancer of the Gastroesophageal Junction is Associated with an Increased Expression of Immune Checkpoint Inhibitors-Comparison Against a Therapy Naïve Cohort.

新辅助治疗的胃癌和胃食管连接部癌的治疗耐药性与免疫检查点抑制剂的表达增加相关-与初治队列的比较。

  • 影响因子:3.30
  • DOI:10.1016/j.tranon.2019.11.004
  • 作者列表:"Schoop H","Bregenzer A","Halske C","Behrens HM","Krüger S","Egberts JH","Röcken C
  • 发表时间:2020-02-01
Abstract

: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.

摘要

: 最近的研究揭示了胃癌 (GC) 中免疫检查点调节剂的复杂景观, 我们旨在表征 T 细胞活化的检查点蛋白 V 结构域 Ig 抑制因子 (VISTA) 、程序性细胞死亡 1 配体 1 (PD-L1) 的表达, 和程序性细胞死亡蛋白-1 (PD-1)在以铂类为基础的新辅助化疗后 GCs 的队列研究中。使用免疫组织化学共评估了 141 例 GC 样本、 93 例淋巴结转移和 15 例远处转移。染色结果与临床病理患者特征、遗传改变和生存相关。在 38 例 (30.9%) GCs 的肿瘤细胞和 139 例 (98.6%) GCs 的免疫细胞中检测到 VISTA 的表达。在 27 例 (22.7%) GCs 的肿瘤细胞和 134 例 (96.4%) GCs 的免疫细胞中检测到 PD-L1 的表达。仅在 123 (87.2%) GCs 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 的表达相关,并与肿瘤消退不良相关。与一个古老的治疗初治 GCs 队列相比,我们观察到整体免疫细胞密度显著增加,伴随着 PD-1 和 VISTA 阳性免疫细胞的比例增加。还发现肿瘤细胞中 VISTA 表达的频率大幅增加。新佐剂治疗后,PD-L1 在免疫细胞和肿瘤细胞中表达降低。因此,使用单一 (仅 VISTA 或 PD-L1) 或联合 (VISTA 和 PD-L1) 免疫逃避机制的 GCs 子集可能受益于 anti-PD-L1/抗 VISTA 靶向治疗。

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