引用文本：陈瑞平, 曾博. 2025年食管癌免疫治疗研究前沿与临床转化：基于动态生物标志物的全程分层与联合策略优化[J/CD]. 消化肿瘤杂志（电子版）, 2026, 18(2): 225-233.

作者：陈瑞平，曾博

单位：中山大学附属第一医院胸外科，广东 广州 510080

Authors：Chen Ruiping, Zeng Bo

Unit：Department of Thoracic Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, Guangdong, China

摘要：

食管鳞状细胞癌（esophageal squamous cell carcinoma, ESCC）是食管癌中常见的病理类型，以其高度侵袭性、显著的肿瘤异质性和不良预后为临床特征。随着免疫检查点抑制剂循证证据的不断积累，截至2025年，ESCC的研究重心已从既往免疫治疗可行性的验证，系统转向人群精准筛选、治疗时序优化及联合治疗策略的机制性迭代，旨在实现疗效提升与毒性管理之间的最佳平衡。本文系统梳理了近期食管癌（尤其是ESCC）综合治疗领域的四大关键进展。首先，动态生物标志物的引入推动了治疗策略从“静态分层”向“自适应管理”的跃迁。循环肿瘤DNA（circulating tumor DNA, ctDNA）凭借其对分子响应的实时监测能力，成为预测病理完全缓解及支持器官保留策略决策的重要工具；外泌体程序性死亡受体配体1（exosomal programmed death-ligand 1, ExoPD-L1）作为免疫微环境的动态指标，则为评估免疫耐药提供了新的视角。其次，围手术期治疗模式持续优化，“去放疗”趋势下的新辅助免疫联合化学治疗与保留放射治疗但进行剂量优化的新辅助免疫联合放化疗，在安全性与局部控制之间达成新的平衡，推动治疗路径向多元化发展。再次，在晚期一线治疗中，策略已由“单免疫联合”演进为“双重靶向”协同模式，双特异性抗体[如靶向程序性死亡受体1（programmed death-1, PD-1）/细胞毒性T淋巴细胞相关蛋白4、PD-1/血管内皮生长因子]及新型免疫检查点抑制剂[如靶向T细胞免疫球蛋白和ITIM结构域蛋白（T-cell immunoreceptor with Ig and ITIM domains, TIGIT）]通过空间协同效应与机制互补，逐步突破传统治疗的疗效瓶颈。最后，后线治疗格局因抗体偶联药物（antibody-drug conjugate, ADC）的快速进展而发生重塑，新一代ADC在部分突破人表皮生长因子受体2（human epidermal growth factor receptor 2, HER2）等靶点表达限制的基础上，利用“旁观者效应”及其与免疫治疗的协同作用，为应对获得性耐药提供了新策略。综上，当前食管癌的治疗体系正迈入以生物标志物为导向、机制互补为驱动的精准医学新阶段。未来研究应聚焦于诊疗流程的规范化整合与真实世界验证，以实现患者生存获益的最大化。

关键词：食管鳞状细胞癌；免疫治疗；循环肿瘤DNA；围手术期治疗；双特异性抗体；抗体偶联药物

Abstract：

Esophageal squamous cell carcinoma (ESCC) is a common histological subtype of esophageal cancer, clinically characterized by high aggressiveness, significant tumor heterogeneity, and poor prognosis. With the accumulating evidence for immune checkpoint inhibitors (ICIs), by 2025, the therapeutic focus in ESCC has systematically shifted from verifying the feasibility of immunotherapy to precise patient screening, optimization of treatment timing, and mechanistic iteration of combinatorial strategies. The ultimate goal is to achieve an optimal balance between enhanced efficacy and toxicity management. This article systematically summarizes four key advances in the comprehensive treatment of esophageal cancer (particularly ESCC). First, the introduction of dynamic biomarkers has driven a paradigm shift from static stratification to adaptive management. Circulating tumor DNA (ctDNA), with its capacity for real-time monitoring of molecular response, has emerged as a critical tool for predicting pathological complete response (pCR) and supporting decision-making in organ preservation strategies. Meanwhile, exosomal programmed death-ligand 1 (ExoPD-L1), serving as a dynamic indicator of the immune microenvironment, offers novel perspectives for assessing immune resistance. Second, perioperative treatment models continue to evolve. Neoadjuvant immunochemotherapy (nICT), reflecting a “radiotherapy-sparing” trend, and neoadjuvant chemoradiotherapy plus immunotherapy (nICRT) with optimized dosing, have achieved a new equilibrium between safety and local control, promoting the diversification of therapeutic pathways. Third, in the advanced first-line setting, strategies have evolved from “single-agent immunotherapy combinations” to “dual-targeting” synergistic models. Bispecific antibodies [e.g., targeting programmed death-1 (PD-1)/cytotoxic T lymphocyte-associated protein-4 (CTLA-4), PD-1/vascular endothelial growth factor (VEGF)] and novel checkpoint inhibitors [e.g., anti-T-cell immunoreceptor with Ig and ITIM domains (TIGIT)] are progressively breaking through efficacy bottlenecks via spatial synergy and mechanistic complementarity. Finally, the landscape of later-line treatment is being reshaped by rapid advancements in antibody-drug conjugates (ADCs). New-generation ADCs, partially overcoming limitations related to target expression [such as human epidermal growth factor receptor 2 (HER2)], provide novel strategies for managing acquired resistance by leveraging the “bystander effect” and synergy with immunotherapy. In summary, the current treatment paradigm for esophageal cancer is entering a new era of precision medicine driven by biomarker guidance and mechanistic complementarity. Future research should focus on the standardized integration of diagnostic and therapeutic workflows and real-world validation to maximize patient survival benefits.

Key words：Esophageal squamous cell carcinoma; Immunotherapy; Circulating tumor DNA; Perioperative treatment; Bispecific antibodies; Antibody-drug conjugates

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