PD-1 blockade and CDK4/6 inhibition augment nonoverlapping features of T cell activation in cancer

J Exp Med. 2023 Apr 3;220(4):e20220729. doi: 10.1084/jem.20220729. Epub 2023 Jan 23.

Abstract

We performed single-cell RNA-sequencing and T cell receptor clonotype tracking of breast and ovarian cancer patients treated with the CDK4/6 inhibitor ribociclib and PD-1 blockade. We highlight evidence of two orthogonal treatment-associated phenomena: expansion of T cell effector populations and promotion of T cell memory formation. Augmentation of the antitumor memory pool by ribociclib boosts the efficacy of subsequent PD-1 blockade in mouse models of melanoma and breast cancer, pointing toward sequential therapy as a potentially safe and synergistic strategy in patients.

Publication types

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

MeSH terms

  • Aminopyridines / pharmacology
  • Animals
  • Melanoma*
  • Mice
  • Programmed Cell Death 1 Receptor*
  • Purines

Substances

  • ribociclib
  • Programmed Cell Death 1 Receptor
  • Aminopyridines
  • Purines