Empowering hypoxia to convert cold tumors into hot tumors for breast cancer immunotherapy.

IF 7 2区生物学 Q1 CELL BIOLOGY

Cell Death Discovery Pub Date : 2025-08-14 DOI:10.1038/s41420-025-02682-8

Lu Liu, Danping Wu, Zhiwen Qian, Ying Jiang, Yilan You, YiDa Wang, Feng Zhang, Xin Ning, Jie Mei, Jabed Iqbal, Yanfang Gu, Yan Zhang

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Abstract

Breast cancer remains the most common cancer among women globally and a leading cause of cancer-related death. Despite the promise of immunotherapy for triple-negative breast cancer (TNBC), its overall effectiveness is hindered by the cold tumor microenvironment (TME), characterized by sparse immune cell infiltration. This review explores the pivotal role of hypoxia in shaping the breast cancer TME and its influence on immunotherapy efficacy. As a defining feature of most solid tumors, including breast cancer, hypoxia drives aggressive tumor behavior, metastasis, and treatment resistance. The hypoxic TME promotes immune evasion and maintains the cold tumor phenotype. Targeting hypoxia offers a potential strategy for transforming cold breast tumors into hot tumors that respond more effectively to immunotherapy. This review consolidates existing insights into the interplay between hypoxia, tumor immunophenotypes, and immunotherapy in breast cancer. By analyzing the mechanisms through which hypoxia modulates the TME and immune response, it proposes innovative strategies to enhance immunotherapy outcomes. This comprehensive analysis lays the groundwork for developing more effective combination therapies to improve breast cancer prognosis.

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利用缺氧将冷肿瘤转化为热肿瘤用于乳腺癌免疫治疗。

乳腺癌仍然是全球妇女中最常见的癌症，也是癌症相关死亡的主要原因。尽管免疫疗法有望治疗三阴性乳腺癌（TNBC），但其整体效果受到以免疫细胞浸润稀疏为特征的冷肿瘤微环境（TME）的阻碍。本文就缺氧在乳腺癌TME形成中的关键作用及其对免疫治疗效果的影响进行综述。作为包括乳腺癌在内的大多数实体肿瘤的一个决定性特征，缺氧驱动肿瘤的侵袭性行为、转移和治疗抵抗。低氧TME促进免疫逃避，维持冷瘤表型。靶向缺氧提供了将冷性乳腺肿瘤转化为对免疫治疗反应更有效的热性肿瘤的潜在策略。这篇综述巩固了现有的关于缺氧、肿瘤免疫表型和乳腺癌免疫治疗之间相互作用的见解。通过分析缺氧调节TME和免疫反应的机制，提出提高免疫治疗效果的创新策略。这项综合分析为开发更有效的联合疗法以改善乳腺癌预后奠定了基础。

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

Cell Death Discovery Biochemistry, Genetics and Molecular Biology-Cell Biology

CiteScore

8.30

自引率

1.40%

发文量

468

审稿时长

9 weeks

期刊介绍： Cell Death Discovery is a multidisciplinary, international, online-only, open access journal, dedicated to publishing research at the intersection of medicine with biochemistry, pharmacology, immunology, cell biology and cell death, provided it is scientifically sound. The unrestricted access to research findings in Cell Death Discovery will foster a dynamic and highly productive dialogue between basic scientists and clinicians, as well as researchers in industry with a focus on cancer, neurobiology and inflammation research. As an official journal of the Cell Death Differentiation Association (ADMC), Cell Death Discovery will build upon the success of Cell Death & Differentiation and Cell Death & Disease in publishing important peer-reviewed original research, timely reviews and editorial commentary. Cell Death Discovery is committed to increasing the reproducibility of research. To this end, in conjunction with its sister journals Cell Death & Differentiation and Cell Death & Disease, Cell Death Discovery provides a unique forum for scientists as well as clinicians and members of the pharmaceutical and biotechnical industry. It is committed to the rapid publication of high quality original papers that relate to these subjects, together with topical, usually solicited, reviews, editorial correspondence and occasional commentaries on controversial and scientifically informative issues.