CDK4/6 Inhibition Augments Antitumor Immunity by Enhancing T-cell Activation

Abstract Immune checkpoint blockade, exemplified by antibodies targeting the PD-1 receptor, can induce durable tumor regressions in some patients. To enhance the efficacy of existing immunotherapies, we screened for small molecules capable of increasing the activity of T cells suppressed by PD-1. Here, we show that short-term exposure to small-molecule inhibitors of cyclin-dependent kinases 4 and 6 (CDK4/6) significantly enhances T-cell activation, contributing to antitumor effects in vivo, due in part to the derepression of NFAT family proteins and their target genes, critical regulators of T-cell function. Although CDK4/6 inhibitors decrease T-cell proliferation, they increase tumor infiltration and…

• DR
  Damon Runyon Cancer Research Foundation

  Award: DRG-2270-16
• DC
  Dana-Farber Cancer Institute
• GT
  G1 Therapeutics
• NC
  National Cancer Institute

  Awards: 5R01CA122794-10, 5R01CA163896-04, 5R01CA140594-07, CA154303-05, P01CA120964, 5R01CA166480-04, CA179483-03