The landscape of cyclin-dependent kinase 4/6 inhibitors in solid malignancies: emphasis on immunotherapy...

Area of Science:

• Oncology
• Immunology
• Pharmacology

Background:

• Deregulation of Cyclin-Dependent Kinase 4/6 (CDK4/6) is crucial in various cancers.
• CDK4/6 inhibitors are established cancer therapeutics, primarily known for antiproliferative effects.
• Emerging evidence highlights significant immunomodulatory properties of CDK4/6 inhibitors.

Purpose of the Study:

• To explore the immunomodulatory potential of CDK4/6 inhibitors.
• To investigate the synergy between CDK4/6 inhibitors and immune checkpoint inhibitors (ICIs).
• To review the clinical applications of CDK4/6 inhibitors in solid tumors, focusing on ICI combinations.

Main Methods:

• Analysis of preclinical data on CDK4/6 inhibitors' effects on tumor immunity.
• In silico analysis of CDK4/6 inhibitor targets within immune-related pathways.
• Review of clinical data and the Human Protein Atlas for target expression in immune cells.

Main Results:

• CDK4/6 inhibitors enhance tumor antigen presentation and reduce immunosuppressive regulatory T-cells.
• These inhibitors promote memory T-cell development in preclinical models and cancer patients.
• In silico analysis identified 225 targets in 57 immune pathways, with 24 highly expressed in immune cells.

Conclusions:

• CDK4/6 inhibitors possess significant immunomodulatory effects, particularly on T-cell immunity.
• These immune effects suggest a strong rationale for combining CDK4/6 inhibitors with immunotherapies like ICIs.
• Combinations of CDK4/6 inhibitors with ICIs represent a promising therapeutic strategy across various solid malignancies.