Immunomodulation by anticancer cell cycle inhibitors

• Published in: Nature reviews. Immunology Vol. 20; no. 11; pp. 669 - 679
• Main Authors: Petroni, Giulia, Formenti, Silvia C., Chen-Kiang, Selina, Galluzzi, Lorenzo
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.11.2020; Nature Publishing Group
• Subjects: 631/250/2152; 631/250/251; 631/250/262; 631/250/580; Animals; Antineoplastic Agents, Immunological - therapeutic use; Antitumor activity; B cells; Biomedical and Life Sciences; Biomedicine; Breast cancer; Cancer; Care and treatment; Cell cycle; Cell Cycle - drug effects; Cell Cycle Proteins - antagonists & inhibitors; Cell proliferation; Clinical Trials as Topic; Cyclin-dependent kinase 4; Cyclin-Dependent Kinase 4 - antagonists & inhibitors; Cyclin-Dependent Kinase 6 - antagonists & inhibitors; Cyclin-dependent kinases; Health aspects; Humans; Immune response; Immunology; Immunomodulation; Immunostimulation; Inhibitors; Kinases; Neoplasms - drug therapy; Protein Kinase Inhibitors - therapeutic use; Proteins; Review Article; Tumors
• ISSN: 1474-1733; 1474-1741
• DOI: 10.1038/s41577-020-0300-y

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. The clinical activity of cyclin-dependent kinase 4 (CDK4)/CDK6 inhibitors has largely been attributed to their capacity to block the proliferation of tumour cells, but increasing evidence discussed in this Review suggests that these inhibitors also have immunomodulatory effects that promote antitumour immune responses.