Ali et al. performed scRNA- and TCR-seq of circulating T cells and TILs taken pre- and post-first treatment of six patients with metastatic breast or ovarian cancer in a phase I trial of a CDK4/6 inhibitor + anti-PD-1 antibody. Regardless of clinical outcome, combination therapy induced clonal expansion of pre-existing Teff cells (attributed to anti-PD-1 Ab) and expression of novel clonotypes (skewing tumor-specific) and genes associated with stem-like and memory T cells (attributed to iCDK4/6). In melanoma and breast cancer models, survival was enhanced when memory T cells generated in a CDK4/6-inhibited milieu were reinvigorated by subsequent anti-PD-1 treatment.
Contributed by Paula Hochman
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.
Author Info: (1) Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute , Boston, MA, USA. ROR: https://ror.org/02jzgtq86 Department of Immunology, Harvard Medical School ,
Author Info: (1) Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute , Boston, MA, USA. ROR: https://ror.org/02jzgtq86 Department of Immunology, Harvard Medical School , Boston, MA, USA. (2) Department of Medical Oncology, Dana-Farber Cancer Institute , Boston, MA, USA. Department of Medicine, Harvard Medical School , Boston, MA, USA. (3) Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute , Boston, MA, USA. ROR: https://ror.org/02jzgtq86 Department of Immunology, Harvard Medical School , Boston, MA, USA. (4) Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute , Boston, MA, USA. ROR: https://ror.org/02jzgtq86 (5) Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute , Boston, MA, USA. ROR: https://ror.org/02jzgtq86 Department of Medicine, Division of Gastroenterology, Massachusetts General Hospital , Boston, MA, USA. ROR: https://ror.org/002pd6e78 (6) Department of Medicine, Harvard Medical School , Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Massachusetts General Hospital , Boston, MA, USA. ROR: https://ror.org/002pd6e78 (7) Peter MacCallum Cancer Centre , Melbourne, Australia. ROR: https://ror.org/02a8bt934 The Sir Peter MacCallum Department of Oncology, University of Melbourne , Melbourne, Australia. (8) Department of Medical Oncology, Dana-Farber Cancer Institute , Boston, MA, USA. Department of Medicine, Harvard Medical School , Boston, MA, USA. (9) Department of Medical Oncology, Dana-Farber Cancer Institute , Boston, MA, USA. Department of Medicine, Harvard Medical School , Boston, MA, USA. (10) Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute , Boston, MA, USA. ROR: https://ror.org/02jzgtq86 Department of Immunology, Harvard Medical School , Boston, MA, USA.
