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头颈部鳞状细胞癌中的免疫逃逸:肿瘤微环境中癌相关成纤维细胞、免疫检查点与 TP53 突变的作用

英文原题:Immune Evasion in Head and Neck Squamous Cell Carcinoma: Roles of Cancer-Associated Fibroblasts, Immune Checkpoints, and TP53 Mutations in the Tumor Microenvironment.

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Immune Evasion in Head and Neck Squamous Cell Carcinoma: Roles of Cancer-Associated Fibroblasts, Immune Checkpoints, and TP53 Mutations in the Tumor Microenvironment.

PubMed 2025/08/07(内容时间) Cancers (Basel) Q2 · IF 4.8(JCR 2025)

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中文摘要

头颈部鳞状细胞癌(HNSCC)是一种高度侵袭性恶性肿瘤,其肿瘤微环境(TME)中复杂的相互作用会促进免疫逃逸和肿瘤进展。TME 包含癌相关成纤维细胞、免疫细胞、内皮细胞及细胞外基质等多种成分,共同调节肿瘤生长、转移和治疗耐药。HNSCC 通过多种机制实现免疫逃逸,包括抑制细胞毒性 T 淋巴细胞、募集调节性 T 细胞和髓源性抑制细胞等免疫抑制细胞,以及上调 PD-1/PD-L1 和 CTLA-4 等免疫检查点分子。自然杀伤(NK)细胞在抗肿瘤免疫中发挥重要作用,但在 HNSCC TME 中常因抑制性信号和代谢限制而功能障碍。

此外,内皮细胞促进肿瘤血管生成和免疫抑制,进一步加剧疾病进展。免疫治疗的最新进展,尤其是免疫检查点抑制剂和 NK 细胞策略,有望恢复抗肿瘤免疫。HNSCC 中常见的 TP53 突变会影响肿瘤行为和治疗应答,凸显个体化治疗的必要性。本综述全面分析 HNSCC 免疫逃逸的分子和细胞机制,并聚焦旨在改善患者结局的新型治疗策略。

展开英文摘要原文

Head and neck squamous cell carcinoma (HNSCC) is a highly aggressive malignancy characterized by complex interactions within the tumor microenvironment (TME) that facilitate immune evasion and tumor progression. The TME consists of diverse cellular components, including cancer-associated fibroblasts, immune and endothelial cells, and extracellular matrix elements, that collectively modulate tumor growth, metastasis, and resistance to therapy.

Immune evasion in HNSCC is orchestrated through multiple mechanisms, including the suppression of cytotoxic T lymphocytes, recruitment of immunosuppressive cells, such as regulatory T and myeloid-derived suppressor cells, and upregulation of immune checkpoint molecules (e. g. , PD-1/PD-L1 and CTLA-4). Natural killer (NK) cells, which play a crucial role in anti-tumor immunity, are often dysfunctional within the HNSCC TME due to inhibitory signaling and metabolic constraints.

Additionally, endothelial cells contribute to tumor angiogenesis and immune suppression, further exacerbating disease progression. Recent advancements in immunotherapy, particularly immune checkpoint inhibitors and NK cell-based strategies, have shown promise in restoring anti-tumor immunity.

Moreover, TP53 mutations, frequently observed in HNSCC, influence tumor behavior and therapeutic responses, highlighting the need for personalized treatment approaches. This review provides a comprehensive analysis of the molecular and cellular mechanisms governing immune evasion in HNSCC with a focus on novel therapeutic strategies aimed at improving patient outcomes.

论文信息

作者
Tsai CC、Hsu YC、Chu TY、Hsu PC、Kuo CY
第一作者单位
Department of Research, Taipei Tzu Chi Hospital, The Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan.Taiwan
通讯作者单位
Institute of Oral Medicine and Materials, College of Medicine, Tzu Chi University, Hualien 970, Taiwan.Taiwan
文献类型
综述
期刊
Cancers2025 Aug 7
原文标识
PubMed 40805285 · DOI 10.3390/cancers17152590