CDK4/6 Inhibitor Priming Enhances PD-1 Blockade via Sell^hi Neutrophil-Induced Stat5a⁺ Progenitor Exhausted CD8⁺ T Cell.

ABSTRACT: Cell cycle pathway, especially via cyclin D1-CDK4/6 signaling, is enriched in immunotherapy-resistant and immune-excluded tumors. CDK4/6 inhibitor (CDK4/6i) induces antitumor immune phenotypes by targeting both tumor and immune cells, enhancing immune checkpoint blockade (ICB), but optimal combination modalities and the corresponding cellular mechanisms remain unclear. Here, it is shown that activation of tumor cell-intrinsic cyclin D1-CDK4/6 signaling is associated with low tumor-infiltrating lymphocyte populations and immunotherapy resistance in head and neck squamous cell carcinoma (HNSCC). Comparison of sequential versus combinatorial regimens in subcutaneous or orthotopic HNSCC mice revealed that CDK4/6i priming before anti-PD-1 enhances response durability by promoting CD8⁺

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC12667468 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature