联合抗血管生成、免疫检查点抑制剂与化疗在局部进展期胃癌新辅助治疗中的临床意义

Clinical significance of combination of anti⁃angiogenesis,immune checkpoint inhibitors and chemotherapy in the neoadjuvant treatment of locally advanced gastric cancer

联合抗血管生成、免疫检查点抑制剂(ICIs)与化疗(靶-免-化)方案在胃癌的综合治疗中已取得初步成效。实验研究表明,在肿瘤免疫治疗的各种决定因素中,肿瘤微环境(TME)影响ICIs疗效至关重要。导致免疫抑制性TME生物学机制是多因素且十分复杂,但其中较明确和重要的机制之一是肿瘤异常新血管生成的影响。使用小剂量靶向肿瘤血管生成药物(抗VEGF/VEGFR单抗等)有望促使肿瘤血管正常化,逆转免疫抑制性TME为免疫支持性TME,以更好地发挥ICI与化疗药物的协同、互补与增效抗肿瘤作用。对局部进展期胃癌(LAGC)病人开展积极的围术期综合治疗,已成为胃癌外科综合治疗中不可或缺的重要手段。近年来,临床上联合抗血管生成、免疫检查点抑制剂与化疗(靶-免-化)方案应用在LAGC围术期治疗上,初步疗效[病理完全缓解(pCR)、主要病理缓解(MPR)、肿瘤退缩分级(TRG)与治疗相关不良事件(TRAEs)等]显示出令人鼓舞的结果。本文复习有关临床研究结果,作汇总与分析。

The combination of anti‑angiogenesis,immune checkpoint inhibitors(ICIs)and chemotherapy(targetimmune‑chemo)has achieved initial results in the comprehensive treatment of gastric cancer.Experimental studies have shown that among various determinants of tumor immunotherapy,tumor microenvironment(TME)plays a crucial role in affecting ICIs efficacy.The biological mechanism leading to immunosuppressive TME is multi‑factorial and very complex,but one of clear and important mechanisms is the influence of abnormal neoangiogenesis in tumors.The use of low‑dose targeted tumor angiogenesis drugs(such as anti‑VEGF/VEGFR monoclonal antibody,etc.)is expected to make tumor vessels normalization and reverse immunosuppressive TME to immunesupportive TME,so as to play synergistic,complementary,anti‑tumor effects with ICIs and chemotherapy drugs.Perioperative treatment of locally advanced gastric cancer(LAGC)has become an indispensable and important strategy in surgical comprehensive treatment of gastric cancer.In recent years,a therapeutic combination regimen of anti‑angiogenesis,ICIs and chemotherapy(target‑immune‑chemo)has been clinically applied in the perioperative treatment of LAGC,and the preliminary efficacy[pathologic complete response(pCR),major pathological response(MPR),tumor regression grade(TRG)and treatment‑related adverse events(TRAEs),etc.]has shown encouraging results.This article reviewed the relevant clinical research results and made a summary and analysis.