PD-1 blockade and CDK4/6 inhibition augment nonoverlapping features of T cell activation in cancer.
Lestat R AliAna Christina Garrido-CastroPatrick J LenehanNaima BollenrucherCourtney T S KureshiMichael L DouganShom GoelGeoffrey I ShapiroSara M TolaneyStephanie K DouganPublished in: The Journal of experimental medicine (2023)
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.
Keyphrases
- single cell
- cell cycle
- end stage renal disease
- rna seq
- working memory
- ejection fraction
- newly diagnosed
- mouse model
- papillary thyroid
- high throughput
- regulatory t cells
- squamous cell carcinoma
- stem cells
- dendritic cells
- cell proliferation
- combination therapy
- immune response
- childhood cancer
- replacement therapy
- skin cancer