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

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.