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解析乳腺癌肿瘤微环境：影响自然杀伤细胞功能的关键因素及治疗策略

Unraveling the breast cancer tumor microenvironment: crucial factors influencing natural killer cell function and therapeutic strategies.

作者信息

Li Feifei, Gao Chunfang, Huang Yan, Qiao Yu, Xu Hongxiao, Liu Sheng, Wu Huangan

机构信息

Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Shanghai Research Institute of Acupuncture and Meridian, Shanghai, China.

出版信息

Int J Biol Sci. 2025 Mar 24;21(6):2606-2628. doi: 10.7150/ijbs.108803. eCollection 2025.

DOI:10.7150/ijbs.108803
PMID:40303301
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12035885/
Abstract

Natural killer (NK) cells have emerged as a novel and effective treatment for breast cancer. Nevertheless, the breast cancer tumor microenvironment (TME) manifests multiple immunosuppressive mechanisms, impeding the proper execution of NK cell functions. This review summarizes recent research on the influence of the TME on the functionality of NK cells in breast cancer. It delves into the effects of the internal environment of the TME on NK cells and elucidates the roles of diverse stromal components, immune cells, and signaling molecules in regulating NK cell activity within the TME. It also summarizes therapeutic strategies based on small-molecule inhibitors, antibody therapies, and natural products, as well as the progress of research in preclinical and clinical trials. By enhancing our understanding of the immunosuppressive TME and formulating strategies to counteract its effects, we could fully harness the therapeutic promise of NK cells in breast cancer treatment.

摘要

自然杀伤（NK）细胞已成为一种新型且有效的乳腺癌治疗方法。然而，乳腺癌肿瘤微环境（TME）表现出多种免疫抑制机制，阻碍了NK细胞功能的正常发挥。本综述总结了近期关于TME对乳腺癌中NK细胞功能影响的研究。它深入探讨了TME内部环境对NK细胞的影响，并阐明了各种基质成分、免疫细胞和信号分子在调节TME内NK细胞活性中的作用。它还总结了基于小分子抑制剂、抗体疗法和天然产物的治疗策略，以及临床前和临床试验的研究进展。通过加深我们对免疫抑制性TME的理解并制定应对其影响的策略，我们可以充分利用NK细胞在乳腺癌治疗中的治疗潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5b5/12035885/dec89ad50b91/ijbsv21p2606g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5b5/12035885/5013a11231a5/ijbsv21p2606g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5b5/12035885/0d9a341c316c/ijbsv21p2606g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5b5/12035885/d824b7ecf490/ijbsv21p2606g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5b5/12035885/7da4d4f06091/ijbsv21p2606g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5b5/12035885/9fb04e7e54fd/ijbsv21p2606g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5b5/12035885/dec89ad50b91/ijbsv21p2606g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5b5/12035885/5013a11231a5/ijbsv21p2606g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5b5/12035885/0d9a341c316c/ijbsv21p2606g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5b5/12035885/d824b7ecf490/ijbsv21p2606g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5b5/12035885/7da4d4f06091/ijbsv21p2606g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5b5/12035885/9fb04e7e54fd/ijbsv21p2606g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5b5/12035885/dec89ad50b91/ijbsv21p2606g006.jpg

相似文献

[1]
Unraveling the breast cancer tumor microenvironment: crucial factors influencing natural killer cell function and therapeutic strategies.

Int J Biol Sci. 2025-3-24

[2]
Natural Killer Cell Interactions With Myeloid Derived Suppressor Cells in the Tumor Microenvironment and Implications for Cancer Immunotherapy.

Front Immunol. 2021

[3]
Cytokines Orchestrating the Natural Killer-Myeloid Cell Crosstalk in the Tumor Microenvironment: Implications for Natural Killer Cell-Based Cancer Immunotherapy.

Front Immunol. 2021-1-29

[4]
Comprehensive single-cell and bulk transcriptomic analyses to develop an NK cell-derived gene signature for prognostic assessment and precision medicine in breast cancer.

Front Immunol. 2024

[5]
Exosomes derived from natural killer cells: transforming immunotherapy for aggressive breast cancer.

Med Oncol. 2025-3-18

[6]
Interleukin signaling in the regulation of natural killer cells biology in breast cancer.

Front Immunol. 2024

[7]
Characterization and Manipulation of the Crosstalk Between Dendritic and Natural Killer Cells Within the Tumor Microenvironment.

Front Immunol. 2021-5-14

[8]
NK Cell Metabolism and Tumor Microenvironment.

Front Immunol. 2019-9-24

[9]
An in vitro model to monitor natural killer cell effector functions against breast cancer cells derived from human tumor tissue.

Methods Cell Biol. 2023

[10]
Metabolic adaptations determine whether natural killer cells fail or thrive within the tumor microenvironment.

Immunol Rev. 2024-5

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本文引用的文献

[1]
Exploring the "chemo" in chemoimmunotherapy for triple-negative breast cancer.

Cancer Cell. 2025-3-10

[2]
Single-cell transcriptomics reveals intratumor heterogeneity and the potential roles of cancer stem cells and myCAFs in colorectal cancer liver metastasis and recurrence.

Cancer Lett. 2025-3-1

[3]
PDPN+ cancer-associated fibroblasts enhance gastric cancer angiogenesis via AKT/NF-κB activation and the CCL2-ACKR1 axis.

MedComm (2020). 2025-1-6

[4]
A Cancer-Specific Anti-Podoplanin Monoclonal Antibody, PMab-117-mG Exerts Antitumor Activities in Human Tumor Xenograft Models.

Cells. 2024-11-6

[5]
Xianling Lianxia formula improves the efficacy of trastuzumab by enhancing NK cell-mediated ADCC in HER2-positive BC.

J Pharm Anal. 2024-10

[6]
Prostaglandin E-EP2/EP4 signaling induces immunosuppression in human cancer by impairing bioenergetics and ribosome biogenesis in immune cells.

Nat Commun. 2024-11-1

[7]
Amphiregulin promotes activated regulatory T cell-suppressive function via the AREG/EGFR pathway in laryngeal squamous cell carcinoma.

Head Face Med. 2024-10-26

[8]
STYK1 mediates NK cell anti-tumor response through regulating CCR2 and trafficking.

J Transl Med. 2024-10-16

[9]
Peripheral NK cell count predicts response and prognosis in breast cancer patients underwent neoadjuvant chemotherapy.

Front Immunol. 2024

[10]
INTASYL self-delivering RNAi decreases TIGIT expression, enhancing NK cell cytotoxicity: a potential application to increase the efficacy of NK adoptive cell therapy against cancer.

Cancer Immunol Immunother. 2024-10-3

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