Immunomodulation by anticancer cell cycle inhibitors

Nat Rev Immunol. 2020 Nov;20(11):669-679. doi: 10.1038/s41577-020-0300-y. Epub 2020 Apr 28.

Abstract

Cell cycle proteins that are often dysregulated in malignant cells, such as cyclin-dependent kinase 4 (CDK4) and CDK6, have attracted considerable interest as potential targets for cancer therapy. In this context, multiple inhibitors of CDK4 and CDK6 have been developed, including three small molecules (palbociclib, abemaciclib and ribociclib) that are currently approved for the treatment of patients with breast cancer and are being extensively tested in individuals with other solid and haematological malignancies. Accumulating preclinical and clinical evidence indicates that the anticancer activity of CDK4/CDK6 inhibitors results not only from their ability to block the cell cycle in malignant cells but also from a range of immunostimulatory effects. In this Review, we discuss the ability of anticancer cell cycle inhibitors to modulate various immune functions in support of effective antitumour immunity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Cell Cycle / drug effects*
  • Cell Cycle Proteins / antagonists & inhibitors*
  • Clinical Trials as Topic
  • Cyclin-Dependent Kinase 4 / antagonists & inhibitors
  • Cyclin-Dependent Kinase 6 / antagonists & inhibitors
  • Humans
  • Immunomodulation*
  • Neoplasms / drug therapy*
  • Protein Kinase Inhibitors / therapeutic use

Substances

  • Antineoplastic Agents, Immunological
  • Cell Cycle Proteins
  • Protein Kinase Inhibitors
  • CDK4 protein, human
  • CDK6 protein, human
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinase 6