Turning cold tumors into hot tumors to ignite immunotherapy

IF 33.9 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Cancer Pub Date : 2025-10-14 DOI:10.1186/s12943-025-02477-6

Yuan-Tong Liu, Yun-Long Wang, Shuo Wang, Jia-Jun Li, Wei He, Xin-Juan Fan, Xiang-Bo Wan

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Abstract

The revolution in cancer immunotherapy, particularly through immune checkpoint inhibitors (ICIs), underscores the significant role of the tumor microenvironment (TME) in determining therapeutic outcomes. At the heart of this is the classification of tumors into “cold” and “hot”, which significantly influences the efficacy of immunotherapy. “Cold” tumors are characterized by scant immune cell infiltration and an immunosuppressive TME, which effectively evades immune detection and resists ICIs. In contrast, “hot” tumors, characterized by abundant immune cells and a proinflammatory environment, are more receptive to immunotherapeutic approaches. This review comprehensively examines the molecular and cellular foundations of the “cold” tumor phenotype, delving into the mechanisms of camouflage (impeding immune priming and infiltration), coercion (suppressing immune functions), and cytoprotection (resisting inflammatory death) that contribute to maintaining immune silence. Furthermore, it critically evaluates emerging strategies for converting “cold” tumors to “hot”, immune-reactive entities, including the role of biomaterials in remodeling the TME to increase the effectiveness of immunotherapy. Through an in-depth exploration of these foundational mechanisms and therapeutic advancements, this review seeks to shed light on the way forward in cancer treatment, framing the transformation of “cold” tumors to “hot” tumors as a crucial approach to enhancing the reach of immunotherapy to a broader array of cancer types.

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将冷肿瘤转化为热肿瘤，点燃免疫疗法

癌症免疫治疗的革命，特别是通过免疫检查点抑制剂（ICIs），强调了肿瘤微环境（TME）在决定治疗结果中的重要作用。其核心是将肿瘤分为“冷”和“热”，这对免疫治疗的效果有很大影响。“冷”肿瘤的特点是缺乏免疫细胞浸润和免疫抑制TME，有效地逃避免疫检测并抵抗ICIs。相反，以丰富的免疫细胞和促炎环境为特征的“热”肿瘤更容易接受免疫治疗方法。本综述全面探讨了“冷”肿瘤表型的分子和细胞基础，深入探讨了伪装（阻碍免疫启动和浸润）、胁迫（抑制免疫功能）和细胞保护（抵抗炎症性死亡）的机制，这些机制有助于维持免疫沉默。此外，它批判性地评估了将“冷”肿瘤转化为“热”免疫反应实体的新兴策略，包括生物材料在重塑TME以提高免疫治疗有效性中的作用。通过对这些基本机制和治疗进展的深入探索，本综述旨在阐明癌症治疗的前进方向，将“冷”肿瘤转化为“热”肿瘤作为增强免疫治疗范围的关键途径，用于更广泛的癌症类型。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Cancer 医学-生化与分子生物学

CiteScore

54.90

自引率

2.70%

发文量

224

审稿时长

2 months

期刊介绍： Molecular Cancer is a platform that encourages the exchange of ideas and discoveries in the field of cancer research, particularly focusing on the molecular aspects. Our goal is to facilitate discussions and provide insights into various areas of cancer and related biomedical science. We welcome articles from basic, translational, and clinical research that contribute to the advancement of understanding, prevention, diagnosis, and treatment of cancer. The scope of topics covered in Molecular Cancer is diverse and inclusive. These include, but are not limited to, cell and tumor biology, angiogenesis, utilizing animal models, understanding metastasis, exploring cancer antigens and the immune response, investigating cellular signaling and molecular biology, examining epidemiology, genetic and molecular profiling of cancer, identifying molecular targets, studying cancer stem cells, exploring DNA damage and repair mechanisms, analyzing cell cycle regulation, investigating apoptosis, exploring molecular virology, and evaluating vaccine and antibody-based cancer therapies. Molecular Cancer serves as an important platform for sharing exciting discoveries in cancer-related research. It offers an unparalleled opportunity to communicate information to both specialists and the general public. The online presence of Molecular Cancer enables immediate publication of accepted articles and facilitates the presentation of large datasets and supplementary information. This ensures that new research is efficiently and rapidly disseminated to the scientific community.