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Tumor Discovery

REVIEW ARTICLE
Emerging immunomodulatory effects of

CDK4/6 inhibitors in breast cancer therapy:
A comprehensive review

2,4
3
2
Yuling Zhang , Bingfeng Chen , Siyue Lin , Rendong Zhang , Jundong Wu *,
1
2
and Chunfa Chen *
2,4
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
(This article belongs to the Special Issue: Advances in Tumor Immune Regulation: Mechanisms and
Therapeutic Insights)

Abstract

Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, initially developed to regulate
cell cycle progression, have recently been recognized as potent immunomodulatory
*Corresponding authors: agents in cancer therapy. Accumulating evidence indicates that these inhibitors can
Jundong Wu
(wujun-dong@163.com) modulate key immune cells, including T cells, natural killer cells, and macrophages,
Chunfa Chen thereby enhancing their antitumor functions. By arresting cell cycle progression
(chenchunfa@stu.edu.cn) in both tumor and immune cells, CDK4/6 inhibitors create an immune-permissive
Citation: Zhang Y, Chen B, Lin S, microenvironment that facilitates more effective immune-mediated tumor
Zhang R, Wu W, Chen C. Emerging eradication. In addition, these inhibitors may help overcome immune resistance
immunomodulatory effects of mechanisms, providing a strong rationale for their combination with immune
CDK4/6 inhibitors in breast cancer
therapy: A comprehensive review. checkpoint inhibitors to amplify antitumor responses. Despite these promising
Tumor Discov. 2025;4(3):16-31. findings, the specific mechanisms through which CDK4/6 inhibitors enhance immune
doi: 10.36922/TD025190037 responses, as well as their potential applications in breast cancer, remain areas of
Received: May 8, 2025 active investigation. A deeper understanding of their immunomodulatory effects
Revised: June 28, 2025 is essential for developing novel combination therapies that could significantly
improve the efficacy of cancer immunotherapy. This review synthesizes the latest
Accepted: July 2, 2025 evidence on the immunomodulatory effects of CDK4/6 inhibitors, highlighting their
Published online: August 7, 2025 potential to augment antitumor immunity and exploring future directions for their
Copyright: © 2025 Author(s). clinical application.
This is an Open-Access article
distributed under the terms of the
Creative Commons Attribution Keywords: CDK4/6 inhibitors; Immunomodulation; Antitumor immunity; Combination
License, permitting distribution, therapy; Cancer treatment
and reproduction in any medium,
provided the original work is
properly cited.
Publisher’s Note: AccScience 1. Introduction
Publishing remains neutral with
regard to jurisdictional claims in
published maps and institutional The field of cancer therapy has undergone remarkable advancements, transitioning
affiliations. from conventional cytotoxic chemotherapy to more precise strategies targeting specific

Volume 4 Issue 3 (2025) 16 doi: 10.36922/TD025190037