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REVIEW ARTICLE

Emerging immunomodulatory effects of CDK4/6 inhibitors in breast cancer therapy: A comprehensive review

Yuling Zhang1 ,  Bingfeng Chen2 ,  Siyue Lin3 ,  Rendong Zhang2 ,  Jundong Wu2,4* ,  Chunfa Chen2,4*
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1 Department of Medical Quality Management, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China
2 The Breast Center, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China
3 First Clinical Medical College of Guangdong Medical University, Zhanjiang, Guangdong, China
4 The Research Laboratory for Breast Cancer Diagnosis and Treatment, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China
Tumor Discovery, 025190037 https://doi.org/10.36922/TD025190037
Received: 8 May 2025 | Revised: 28 June 2025 | Accepted: 2 July 2025 | Published online: 7 August 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, initially developed to regulate cell cycle progression, have recently been recognized as potent immunomodulatory agents in cancer therapy. Accumulating evidence indicates that these inhibitors can modulate key immune cells, including T cells, natural killer cells, and macrophages, thereby enhancing their antitumor functions. By arresting cell cycle progression in both tumor and immune cells, CDK4/6 inhibitors create an immune-permissive microenvironment that facilitates more effective immune-mediated tumor eradication. In addition, these inhibitors may help overcome immune resistance mechanisms, providing a strong rationale for their combination with immune checkpoint inhibitors to amplify antitumor responses. Despite these promising findings, the specific mechanisms through which CDK4/6 inhibitors enhance immune responses, as well as their potential applications in breast cancer, remain areas of active investigation. A deeper understanding of their immunomodulatory effects is essential for developing novel combination therapies that could significantly improve the efficacy of cancer immunotherapy. This review synthesizes the latest evidence on the immunomodulatory effects of CDK4/6 inhibitors, highlighting their potential to augment antitumor immunity and exploring future directions for their clinical application.

Keywords
CDK4/6 inhibitors
Immunomodulation
Antitumor immunity
Combination therapy
Cancer treatment
Funding
None.
Conflict of interest
The authors declare they have no competing interests.
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Tumor Discovery, Electronic ISSN: 2810-9775 Print ISSN: 3060-8597, Published by AccScience Publishing
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