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肿瘤微环境中的免疫调节机制及其在癌症治疗中的应用:从基础研究到临床转化

英文原题:Immune regulatory mechanisms in the tumor microenvironment and their applications in cancer therapy: from basic research to clinical translation.

查看英文原题

Immune regulatory mechanisms in the tumor microenvironment and their applications in cancer therapy: from basic research to clinical translation.

PubMed 2026/05/29(内容时间) Front Immunol Q1 · IF 7(JCR 2025)

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中文摘要

癌症免疫治疗显著推进了肿瘤学诊疗,为一部分患者提供了持久缓解。然而,这些治疗的疗效常常受到肿瘤微环境(TME)所 orchestrate 的原发性和获得性耐药的限制。在高度异质性的 TME 中,肿瘤细胞、基质成分和浸润免疫细胞之间的多向相互作用主动抑制抗肿瘤免疫。本综述全面审视了 TME 内多方面的免疫调节机制,特别关注肿瘤相关巨噬细胞(TAMs)、髓源性抑制细胞(MDSCs)和调节性 T 细胞(Tregs)的免疫抑制作用。

我们进一步探讨代谢重编程——如 Warburg 效应、乳酸积累和缺氧——如何创造一个不利的微环境,损害效应 T 细胞功能并促进免疫逃逸。将基础研究与临床转化相衔接,我们系统评估了当前针对 TME 的治疗策略,包括免疫检查点抑制剂(ICIs)、过继细胞疗法、溶瘤病毒和抗血管生成药物。本综述还强调了旨在重塑免疫抑制性基质和正常化肿瘤血管系统的新兴联合方法。

最后,我们讨论了临床应用中的关键挑战,如肿瘤异质性和对预测性生物标志物的需求,强调针对特定 TME 表型量身定制的个性化策略对于克服治疗耐药和改善患者预后至关重要。

展开英文摘要原文

Cancer immunotherapy has significantly advanced oncological care, offering durable responses for a subset of patients.

However, the efficacy of these treatments is frequently hindered by primary and acquired resistance orchestrated by the tumor microenvironment (TME). Within the highly heterogeneous TME, multidirectional interactions between tumor cells, stromal components, and infiltrating immune cells actively suppress anti-tumor immunity.

This review comprehensively examines the multifaceted immune regulatory mechanisms within the TME, with a specific focus on the immunosuppressive roles of tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), and regulatory T cells (Tregs).

We further explore how metabolic reprogramming-such as the Warburg effect, lactate accumulation, and hypoxia-creates a hostile niche that impairs effector T cell function and promotes immune evasion.

Bridging basic research to clinical translation, we systematically evaluate current TME-targeted therapeutic strategies, including immune checkpoint inhibitors (ICIs), adoptive cell therapies, oncolytic viruses, and anti-angiogenic agents. The review also highlights emerging combinatorial approaches designed to remodel the immunosuppressive stroma and normalize the tumor vasculature.

Finally, we discuss critical challenges in clinical application, such as tumor heterogeneity and the need for predictive biomarkers, emphasizing that personalized strategies tailored to specific TME phenotypes are essential for overcoming therapeutic resistance and improving patient outcomes.

论文信息

作者
Feng Y、Wang Y、Li X、Wang Y、Zhang M
单位
The Second Hospital, Dalian Medical University, Dalian, Liaoning, China.China
文献类型
综述
期刊
Frontiers in immunology2026
原文标识
PubMed 42292456 · DOI 10.3389/fimmu.2026.1810065