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摘要: 食管癌（esophageal cancer，EC）是常见的消化系统恶性肿瘤，主要病理类型分为鳞癌（squamous cell carcinoma，SCC）和腺癌（adenocarcinoma，AC）。EC患者的传统治疗方式包括手术、化疗和放疗。然而，系统治疗仅在部分患者中疗效较好，多数患者在初始治疗后很快复发。免疫检查点抑制剂可以通过重新激活抗肿瘤免疫反应，强化对肿瘤细胞的杀伤效应来发挥作用，从而提高临床疗效。目前，程序性细胞死亡因子-1（programmed death-1，PD-1）抑制剂已成为肿瘤治疗的重要手段之一。PD-1抑制剂在EC中的研究不断增多，尽管临床试验KEYNOTE-181和ATTRACTION-03取得了较好的治疗效果，但是仍需要提高对EC免疫状况的认识，以助于制定更为有效的免疫治疗策略，从而精准选择受益患者。Abstract: As a common tumor of digestive system, esophageal cancer (EC) is histologically classified as either esophageal squamous cell carcinoma (ESCC) or esophageal adenocarcinoma (EAC). Although conventional treatment modalities for EC include surgery, chemotherapy, and radiation, not all patients respond to initial systemic treatments, with a significant proportion of patients experiencing disease recurrence after the initial treatment. Immune checkpoint inhibitors can enhance antitumor adaptive immunity by rejuvenating antitumor immune responses, thereby improving clinical outcomes. In particular, immune checkpoint inhibitors for programmed cell death-1 (PD-1) have emerged as an important treatment modality for several cancer types, with the number of clinical research on PD-1 checkpoint inhibitors for EC constantly increasing. However, despite the good preliminary clinical results of the KEYNOTE-181 and ATTRACTION-03 trials, there is an urgent need to increase awareness regarding the full scope of EC-related immunology background. Only then can we develop more effective immunotherapeutic strategies and accurately select patients who may benefit from PD-1 checkpoint inhibitors.
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表 1 帕博利珠单抗治疗的相关研究
临床试验 病理类型 例数 研究设计 主要结果 3～5级AE KEYNOTE-028 EC 23 帕博利珠单抗单药 总体ORR：30%；ESCC 的ORR：28%，EAC 的ORR：40% 17.0% KEYNOTE-180 EC/EGC 121 帕博利珠单抗 总体ORR：9.9%；ESCC 的 ORR：14.3%，EGC 的 ORR：5.2% 12.4% KEYNOTE-181 EC 628 帕博利珠单抗 vs. 化疗 CPS≥10分的ESCC: mOS：8.2个月 vs. 7.1个月 18.2% vs. 40.9% 1年OS：39.4% vs. 24.9% CPS≥10分的EAC: mOS：6.3个月 vs. 6.9个月 1年OS：23% vs. 15% KEYNOTE-590 EC/EGC 749 帕博利珠单抗联合化疗 vs. 化疗 CPS≥10组OS：13.5个月 vs. 9.4个月 − ESCC亚组OS：13.9个月 vs. 8.8个月 
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表 2 纳武利尤单抗治疗的相关性研究
临床试验 病理类型 例数 研究设计 主要结果 3～5级AE ATTRACTION-01 ESCC 64 纳武利尤单抗单药 ORR：17% 17% mOS：10.8个月 ATTRACTION-03 ESCC 419 纳武利尤单抗vs.单药化疗 ORR：19% vs. 22% 18% vs. 63% mOS：10.9 个月vs. 8.4个月 CheckMate- 577 EC/EGC 794 纳武利尤单抗vs.安慰剂 mDFS：22.4个月 vs. 11.0个月 19% CHECKMate-032 EC/EGC 160 纳武利尤单抗vs.纳武利尤单抗（1 mg/kg）
联合伊匹单抗（3 mg/kg）vs.纳武利尤单抗
（3 mg/kg）联合伊匹单抗（1 mg/kg）ORR:12% vs. 24% vs. 8% 17% vs. 47% vs. 27% 1年PFS：8% vs. 17% vs. 10% 1年OS：39% vs. 35% vs. 24%
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表 3 卡瑞利珠单抗治疗的相关性研究
临床试验 病理类型 例数 研究设计 主要结果 3～5级AE NCT02742935 ESCC 30 卡瑞利珠单抗单药 ORR：33.3% 10% mPFS：3.6个月 ESCORT ESCC 457 卡瑞利珠单抗vs.化疗 mOS：8.3个月 vs. 6.2个月 25% vs. 39% ORR：20.2% vs. 6.4% NCT03603756 ESCC 30 卡瑞利珠单抗联合阿帕替尼联合化疗 ORR：80% 20% DCR：96.7% mPFS：6.85个月
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