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

2023/01/23 by Lestat R. Ali, Ana C. Garrido-Castro, Patrick J. Lenehan +8 · 23 citations
Medicine · Biochemistry, Genetics and Molecular Biology · #Cancer Immunotherapy and Biomarkers #Advanced Breast Cancer Therapies #Cancer Genomics and Diagnostics

paper · doi:10.1084/jem.20220729

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.

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