To cycle or fight - CDK 4/6 inhibitors at the crossroads of anti-cancer immunity

Dysregulation of cell division resulting in aberrant cell proliferation is a key hallmark of cancer, making it a rational and important target for innovative anti-cancer drug development. Three selective CDK4/6 inhibitors are FDA and EMEA approved for hormone receptor positive/HER2 negative advanced breast cancer. A major emerging appreciation is that these inhibitors are not only cytostatic, but also play critical roles in the interaction between tumour cells and the host immune response. However, to trigger an effective immune response, lymphocytes must also proliferate. This review aims to assimilate our emerging understanding on the role of CDK4/6 inhibitors in cell cycle control, as well as their biological effect on T cells and other key immune cells, and the confluence of preclinical evidence of augmentation of anti-cancer immunity by these drugs. We aim to provide a framework for understanding the role of the cell cycle in anti-cancer immunity, discussing ongoing clinical trials evaluating this concept and challenges for developing rational combinations with immune-therapy.

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