Avgustinovich Alexandra V, Bakina Olga V, Afanas'ev Sergey G, Spirina Liudmila V, Volkov Alexander M
Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, 5 Kooperativny Street, Tomsk 634050, Russia.
Institute of Strength Physics and Materials Science of the Siberian Branch of the Russian Academy of Sciences, 2/4 pr. Akademicheskii, Tomsk 634055, Russia.
Curr Issues Mol Biol. 2023 Sep 19;45(9):7642-7649. doi: 10.3390/cimb45090481.
The landscape of gastric cancer treatment has changed owing to the widespread use of immune checkpoint inhibitors. Autophagy, involved in regulating the immune system, is a potential trigger of immunity in tumors. This study aims to find molecular-based evidence for the effectiveness of FLOT chemotherapy with immune checkpoint inhibitors in gastric cancer patients.
Three patients with advanced gastric cancer received FLOT neoadjuvant chemotherapy with immunotherapy and surgery. IHC was used to determine the PD-L1 status. Real-time PCR was used to analyze expression patterns of transcriptional growth factors, AKT/mTOR signaling components, PD-1, PD-L1, PD-L2 and LC3B. The LC3B content was measured via Western blotting analysis.
The combination of FLOT neoadjuvant chemotherapy and immunotherapy was found to be efficient in patients with a PD-L1-positive status. Gastric tumors with a PD-L1-positive status exhibited autophagy activation and decreased PD-1 expression.
FLOT chemotherapy combined with immune checkpoint inhibitors showed high efficacy in gastric cancer patients with a positive PD-L1 status. Autophagy was involved in activating the tumor immunity. Further research is needed to clarify the mechanism of effective anticancer treatment.
由于免疫检查点抑制剂的广泛应用，胃癌治疗格局已发生改变。自噬参与调节免疫系统，是肿瘤免疫的潜在触发因素。本研究旨在寻找基于分子的证据，以证明氟尿嘧啶、亚叶酸钙、奥沙利铂和多西他赛（FLOT）化疗联合免疫检查点抑制剂对胃癌患者的有效性。
三名晚期胃癌患者接受了FLOT新辅助化疗联合免疫治疗及手术。采用免疫组化法测定程序性死亡受体配体1（PD-L1）状态。采用实时聚合酶链反应分析转录生长因子、蛋白激酶B（AKT）/哺乳动物雷帕霉素靶蛋白（mTOR）信号通路成分、程序性死亡受体1（PD-1）、PD-L1、程序性死亡受体配体2（PD-L2）和微管相关蛋白1轻链3β（LC3B）的表达模式。通过蛋白质免疫印迹分析测定LC3B含量。
发现FLOT新辅助化疗与免疫治疗联合应用对PD-L1阳性患者有效。PD-L1阳性的胃肿瘤表现出自噬激活和PD-1表达降低。
FLOT化疗联合免疫检查点抑制剂对PD-L1阳性的胃癌患者显示出高效。自噬参与激活肿瘤免疫。需要进一步研究以阐明有效的抗癌治疗机制。
