The role of targeting CDK4/6 in cancer immunotherapy

Abstract

Cyclin-dependent kinase 4/6 (CDK4/6) acts as a crucial point of regulation in the G1-to-S transition in the cell division cycle, its aberrant activation was found in various human cancers, leading to abnormal cell proliferation. Recent clinical trials have reported that combined with other small-molecule targeted therapies, CDK4/6 inhibitors increase overall survival and objective response rates in breast cancer (BC), non-small cell lung cancer (NSCLC), and head and neck squamous cell carcinoma (HNSCC). Notably, targeting CDK4/6 triggers an antitumor immune response, providing a potential combined application method for immunotherapy. In this review, we summarize underlying mechanism of targeting CDK4/6 in regulating antigen presentation, immune cell activation, and tumor immune microenvironment (TIME) remodeling and in producing synergistic effects with immune checkpoint blockade (ICB) in cancer clinical treatment.