摘要
以程序性死亡-1(programmed death-1,PD-1)及程序性死亡配体1(programmed death-ligand 1,PD-L1)等免疫检查点抑制剂为代表的免疫治疗,使多种消化道肿瘤如胃癌、直肠癌、肝癌等能够获得持续缓解和生存获益,尤其是对有转移或者复发的患者获益更多。但并非所有胃肠道肿瘤的患者对抗PD-1和抗PD-L1的治疗均有较好的反应。因此亟需其他生物标志物来识别对治疗有效和无效的患者,以更好地预测其临床疗效。PD-L1的表达已逐渐成为预测免疫治疗疗效的潜在生物标志物,但仅依靠PD-L1不足以对患者可能的临床结果进行分类。其他生物分子,如肿瘤突变负荷(tumor mutational burden,TMB)、微卫星不稳定(microsatellite instability,MSI)及循环肿瘤DNA(circulating tumor DNA,ctDNA)等也在进一步探索中。但由于这些分子自身的局限性,目前在消化系统肿瘤免疫治疗中尚缺乏较好的生物标志物来实现患者识别和筛选,尤其是肝癌。本文将对已发现的生物标志物进行总结,以期为临床治疗和探索其他新的生物标志物奠定基础。
Immunotherapy,which is represented by immune checkpoint inhibitors such as programmed death-1(PD-1)or programmed death-ligand 1(PD-L1)blockades,can provide continuous remission and survival benefits for patients suffering from most digestive tumors,including gastric cancer,colorectal cancer,and hepatocellular cancer(HCC).These effects are especially pronounced for patients with metastasis or recurrence.However,not all patients with gastrointestinal neoplasms respond well to anti-PD-1/PD-L1 agents.Therefore,biomarkers are urgently needed to identify which patients will respond effectively or ineffectively to such treatments,to better predict clinical effects.PD-L1 expression has gradually emerged as a potential biomarker to predict immunotherapy-based efficacy,but PD-L1 alone cannot sufficiently distinguish possible outcomes.Other molecules,such as tumor mutational burden(TMB),microsatellite instability(MSI),and circulating tumor DNA(ctDNA),are now being studied further.Unfortunately,due to their inherent limitations,currently there are no standard or well-established biomarkers in immunotherapy for digestive system tumors,especially for HCC.In this article,we summarize existing biomarkers to lay the foundations for future expectations regarding clinical treatment,and for the exploration of new biomarkers.
作者
陈渝宏
杨彪(综述)
廖正银(审校)
Yuhong Chen;Biao Yang;Zhengyin Liao(Department of Abdominal Oncology,West China Medical School,West China Hospital,Sichuan University,Chengdu 610041,China)
出处
《中国肿瘤临床》
CAS
CSCD
北大核心
2022年第12期631-635,共5页
Chinese Journal of Clinical Oncology
基金
四川省科技厅应用基础研究基金(编号:21YYJC2782)
四川大学华西医院专职博士后研发基金项目(编号:2021HXBH23)资助。
关键词
生物标志物
程序性死亡受体-1
肿瘤突变负荷
微卫星不稳定性
循环肿瘤
DNA
biomarkers
programmed death-ligand 1(PD-L1)
tumor mutational burden(TMB)
microsatellite instability(MSI)
circulating tumor DNA
