Inhibition of CDK4/6 Promotes CD8 T-cell Memory Formation.

ABSTRACT: CDK4/6 inhibitors are approved to treat breast cancer and are in trials for other malignancies. We examined CDK4/6 inhibition in mouse and human CD8⁺ T cells during early stages of activation. Mice receiving tumor-specific CD8⁺ T cells treated with CDK4/6 inhibitors displayed increased T-cell persistence and immunologic memory. CDK4/6 inhibition upregulated MXD4, a negative regulator of MYC, in both mouse and human CD8⁺ T cells. Silencing of Mxd4 or Myc in mouse CD8⁺ T cells demonstrated the importance of this axis for memory formation. We used single-cell transcriptional profiling and T-cell receptor clonotype tracking to evaluate recently activated human CD8⁺ T cells in patients with breast cancer before and during treatment w

SUBMITTER: Heckler M 

PROVIDER: S-EPMC8487897 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature