Abstract
The dysregulation of the cell cycle is one of the hallmarks of cancer. Cyclin-dependent kinase 4 (CDK4) and CDK6 play crucial roles in regulating cell cycle and other cellular functions. CDK4/6 inhibitors have achieved great success in treating breast cancers and are currently being tested extensively in other tumor types as well. Accumulating evidence suggests that CDK4/6 inhibitors exert antitumor effects through immunomodulation aside from cell cycle arrest. Here we outline the immunomodulatory activities of CDK4/6 inhibitors, discuss the immune mechanisms of drug resistance and explore avenues to harness their immunotherapeutic potential when combined with immune checkpoint inhibitors (ICIs) or chimeric antigen receptor (CAR) T-cell therapy to improve the clinical outcomes.