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

The authors use single-cell RNA-sequencing and TCR tracking to analyze blood and tumors from breast and ovarian cancer patients treated with PD-1 blockade and CDK4/6 inhibition. They find that both therapies are immunologically active and enhance T cell effector function and memory, respectively. 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.