收稿日期: 2025-10-24
网络出版日期: 2026-03-26
基金资助
国家自然科学基金项目(82002592);河南省科技厅中原科技创新领军人才项目(234200510006)
Heterogeneity of the immune microenvironment in esophageal squamous cell carcinoma and combination immunotherapy strategies
Received date: 2025-10-24
Online published: 2026-03-26
食管鳞癌（ESCC）是全球范围内发病与死亡率较高的恶性肿瘤，其免疫微环境（tumor immune microenvironment， TIME）具有高度异质性，是导致免疫检查点抑制剂（immune checkpoint inhibitors， ICIs）疗效差异及耐药的核心原因。该文从空间分布、时间动态、细胞组成、功能状态及分子表达等多个层面系统解析了ESCC TIME的多维异质性；针对异质性机制，重点探讨了联合治疗新策略的创新性与实用性，通过免疫联合化疗、放疗、抗血管生成治疗，以及靶向Tregs、巨噬细胞等重塑TIME，逆转免疫抑制，并将“冷肿瘤”转化为“热肿瘤”；此外还强调了基于生物标志物的个体化治疗策略在克服异质性和提升疗效中的关键作用。本文为理解ESCC免疫微环境的复杂性提供了新视角，并为临床实践中制定精准联合免疫治疗方案提供了理论依据与方向。
张瓅方 , 张晖 , 李凯 , 卞华 . 食管鳞癌免疫微环境异质性及免疫治疗联合策略[J]. 实用医学杂志, 2026 , 42(6) : 944 -951 . DOI: 10.3969/j.issn.1006-5725.2026.06.006
Esophageal squamous cell carcinoma （ESCC） is a malignant tumor with high global incidence and mortality. Its tumor immune microenvironment （TIME） is highly heterogeneous， which is a core reason for the varied efficacy and resistance to immune checkpoint inhibitors （ICIs）. This article systematically analyzes the multi-dimensional heterogeneity of the ESCC TIME across several aspects： spatial distribution， temporal dynamics， cellular composition， functional states， and molecular expression. To address the mechanisms of this heterogeneity， we focus on innovative and practical combination strategies. These include combining immunotherapy with chemotherapy， radiotherapy， anti-angiogenic therapy， and novel approaches targeting Tregs， macrophages. These strategies can reshape the TIME， reverse immunosuppression， and convert "cold" tumors into "hot" tumors. Additionally， we emphasize the critical role of biomarker-based individualized treatment strategies in overcoming heterogeneity and improving therapeutic outcomes. This review offers a novel perspective for understanding the complexity of the ESCC immune microenvironment. It also provides a theoretical foundation and direction for developing precise combination immunotherapy regimens in clinical practice.
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