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

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 identified evidence of two orthogonal treatment-associated phenomena: expansion of T cell effector populations and promotion of T cell memory formation. Peripheral blood mononuclear cells (PBMCs) from metastatic breast (n = 5) and ovarian (n = 1) cancer patients were isolated before and after combination treatment with the CDK4/6 inhibitor ribociclib and an anti-PD1 monoclonal antibody. Tumor-infiltrating lymphocytes were also obtained. T cells were sorted by flow cytometry from those samples and subjected to single-cell RNA-sequencing and single-cell TCR-sequencing.