食管鳞癌免疫微环境异质性及免疫治疗联合策略

doi:10.3969/j.issn.1006-5725.2026.06.006

Abstract

Abstract:

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.

Key words: esophagus cancer, squamous-cell carcinoma, tumor immune microenvironment heterogeneity, immunotherapy, immune checkpoint inhibitors, resistance

CLC Number:

R735

Lifang ZHANG,Hui ZHANG,Kai LI,Hua BIAN. Heterogeneity of the immune microenvironment in esophageal squamous cell carcinoma and combination immunotherapy strategies[J]. The Journal of Practical Medicine, 2026, 42(6): 944-951.

Figures/Tables 3

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References 53

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肿瘤区域	主要免疫细胞类型	特征性分子表达	免疫功能状态
侵袭前沿	CAFs，SPP1?巨噬细胞， Tregs	JAG1，NOTCH1，TGF-β，VEGFA	免疫抑制（“冷”微环境）
肿瘤核心	耗竭CD8? T细胞，TAMs	PD-1，TIM-3，LAG-3，IL-10	T细胞功能障碍
TLS	B细胞，Tfh，DCs	CXCL13，CD21，CD23	免疫激活（“热”微环境）

响应类型	治疗前标志	治疗后变化	机制
应答者	CD8?Tex-CXCL13细胞富集	终末耗竭T细胞分化；M1-TAMs↑、成熟DCs↑；微环境类型：“炎症型”；	免疫激活通路增强（如IFN-γ信号）
非应答者	LRRC15?CAFs、SPP1?巨噬细胞富集^[18]	Tregs↑、MDSCs↑；持续免疫抑制；	LRRC15?CAFs分泌IL-6、 TGF-β；SPP1?巨噬细胞通过VEGFA促血管生成和T细胞排斥

Heterogeneity of the immune microenvironment in esophageal squamous cell carcinoma and combination immunotherapy strategies

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