结直肠癌免疫检查点抑制剂治疗现状与展望  

Current status and prospect of immune checkpoint inhibitors for patients with colorectal cancer

作　　者：陈功[1] 张荣欣 李丹丹 王福龙 肖巍魏[1,3] CHEN Gong;ZHANG Rongxin;LI Dandan;WANG Fulong;XIAO Weiwei.(Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou 510060, China)

机构地区：[1]中山大学附属肿瘤医院结直肠外科,广州510060 [2]中山大学附属肿瘤医院生物治疗中心,510060 [3]中山大学附属肿瘤医院放疗科,510060

出　　处：《临床肿瘤学杂志》2020年第10期947-955,共9页Chinese Clinical Oncology

基　　金：百时美施贵宝公司资助

摘　　要：免疫检查点抑制剂(immune checkpoint inhibitors,ICI)的出现为晚期结直肠癌患者带来了新的希望。一方面,DNA错配修复缺陷(mismatch repair defect,dMMR)/高度微卫星不稳定(high microsatellite instability,MSI-H)患者是ICI治疗的“敏感人群”,抗程序性死亡蛋白1(programmed death 1,PD-1)单抗单药可有效用于dMMR/MSI-H转移性结直肠癌患者的后线治疗,在此基础上筛选优势患者人群有利于进一步提高治疗获益。而抗PD-1单抗和低剂量抗细胞毒性T淋巴细胞相关蛋白4(cytotoxic T lymphocyte-associated protein 4,CTLA-4)单抗双药联合方案的疗效优于PD-1单抗单药,安全性可接受,并且有望逐渐拓展至一线治疗甚至更早期疾病的新辅助治疗。另一方面,自2019年起,在ICI用于MMR完整(mismatch repair-proficient,pMMR)/微卫星稳定(microsatellite stability,MSS)结直肠癌患者的治疗方面获得了一些突破,包括寻找潜在有效标志物和不同机制药物的联合治疗等,为这一通常被认为是免疫治疗药物无效的人群带来新的机遇。本文旨在对上述ICI用于结直肠癌患者治疗的现状和最新进展作一综述。The advent of immune checkpoint inhibitors(ICI)has brought new hope to patients with advanced colorectal cancer(CRC).The efficacy of programmed death 1(PD-1)monoclonal antibody monotherapy is evident for treating patients with DNA mismatch repair defect(dMMR)or high microsatellite instability(MSI-H)metastatic CRC that has progressed following first-line chemotherapy.While selection of optimal patient population will help to further improve the treatment benefit.Furthermore,the combination of PD-1 monoclonal antibody and low dose cytotoxic T lymphocyte-associated protein 4(CTLA-4)monoclonal antibody is more efficient for this population with acceptable safety profile,and is hopefully to be used in a broader indication,for instance as a first-line treatment for patients with metastatic diseases,or even as a neoadjuvant therapy for patients in earlier stages.On the other hand,since 2019,some breakthroughs have been achieved in ICIs for patients with mismatch repair-proficient(pMMR)/microsatellite stability(MSS)CRC,who are generally considered intrinsically resistant to ICI monotherapies.These opportunities including potential predictive biomarkers and the combination of agents with different mechanisms.We aim to summarize the current status and the latest developments of the ICIs for the treatment of patients with CRC.

关 键 词：结直肠肿瘤 DNA错配修复 微卫星不稳定性 免疫检查点抑制剂 免疫疗法 

分 类 号：R735.3[医药卫生—肿瘤]