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中华胸部外科电子杂志 ›› 2022, Vol. 09 ›› Issue (02) : 111 -117. doi: 10.3877/cma.j.issn.2095-8773.2022.02.09

综述

食管癌PD-1/PD-L1抑制剂的生物标志物:进展与挑战
喻泊遥1, 刘智超1, 潘杰1, 姜超1, 张龙1, 李志刚1,()   
  1. 1. 200030 上海,上海交通大学医学院附属胸科医院胸外科;200030 上海,上海交通大学医学院附属胸科医院胸部肿瘤研究所
  • 收稿日期:2022-04-10 修回日期:2022-05-05 接受日期:2022-05-18 出版日期:2022-05-28
  • 通信作者: 李志刚

Biomarkers for PD-1/PD-L1 inhibitors in esophageal cancer: progress and challenges

Boyao Yu1, Zhichao Liu1, Jie Pan1, Chao Jiang1, Long Zhang1, Zhigang Li1,()   

  1. 1. Department of Thoracic Surgery, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China; Shanghai Institute of Thoracic Oncology, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China
  • Received:2022-04-10 Revised:2022-05-05 Accepted:2022-05-18 Published:2022-05-28
  • Corresponding author: Zhigang Li
引用本文:

喻泊遥, 刘智超, 潘杰, 姜超, 张龙, 李志刚. 食管癌PD-1/PD-L1抑制剂的生物标志物:进展与挑战[J]. 中华胸部外科电子杂志, 2022, 09(02): 111-117.

Boyao Yu, Zhichao Liu, Jie Pan, Chao Jiang, Long Zhang, Zhigang Li. Biomarkers for PD-1/PD-L1 inhibitors in esophageal cancer: progress and challenges[J]. Chinese Journal of Thoracic Surgery(Electronic Edition), 2022, 09(02): 111-117.

食管癌(EC)是上消化道常见的侵袭性肿瘤,约有70%的患者确诊时癌症已局部或远处转移,预后不佳。目前针对不可切除局部晚期食管癌患者的一线疗法主要为根治性放化疗,大部分患者在1~2年内复发,生存率较低。免疫检查点抑制剂疗法的出现改善了这个局面,2022年版《食管癌治疗指南》首次将免疫检测点抑制剂与化疗联合作为食管癌晚期患者的一线治疗。程序性死亡受体1(PD-1)/程序性死亡配体1(PD-L1)抑制剂是目前免疫疗法在临床试验中最常见的药物,在食管癌中都显示出比传统疗法更好的预后,但是用于筛选PD-1/PD-L1抑制剂获益人群的生物标志物仍是难题。目前通过批准适用于PD-1/PD-L1抑制剂的生物标志物有PD-L1表达,微卫星不稳定性以及肿瘤突变负荷,但以上生物标志物也不能完全保证患者一定获益,也会出现生物标志物未达到患者显著获益的情况。此外部分患者PD-1/PD-L1抑制剂治疗后会出现超进展疾病,导致病情恶化。因此目前需要改善现有的、发现更高预测效能的生物标志物来筛选人群,进一步提升免疫检查点抑制剂在食管癌中的获益。

Esophageal cancer (EC) is a common aggressive tumor of the upper gastrointestinal tract. About 70% of patients have local or distant metastases at diagnosis, and the prognosis is poor. The current first-line therapy for patients with unresectable locally advanced EC is mainly radical chemoradiotherapy, and most patients recur within 1–2 years, with a low survival rate. The advent of immune checkpoint inhibitor therapy has improved this situation. The 2020 Edition of Treatment Guidelines for Esophageal Cancer was the first to add immune checkpoint inhibitor and chemotherapy as first-line treatment for patients with advanced EC. Programmed death 1 (PD-1) /programmed death-ligand 1 (PD-L1) inhibitors are currently the most common drugs in clinical trials for immunotherapy, and all have shown a better prognosis than conventional therapies in esophageal cancer, but the biomarkers used to screen the PD-1/PD-L1 inhibitor benefit population remain challenging. The biomarkers currently approved for PD-1/PD-L1 inhibitors include PD-L1 expression, microsatellite instability, and tumor mutational burden, but these biomarkers do not guarantee a definite benefit, and there are cases where the biomarkers do not achieve a significant benefit for patients. In addition, some patients may develop hyperprogressive disease after PD-1/PD-L1 inhibitor therapy, leading to worsening of the disease. Therefore, there is a need to improve the existing biomarkers and find higher predictive efficacy to screen the population to further enhance the benefit of immune checkpoint inhibitors in esophageal cancer.

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