Trajectories of macrophage ontogeny and reprogramming in cancer.

ABSTRACT: Tumor-associated macrophages (TAMs) often manifest immunosuppressive and tumor-promoting phenotypes contributing to immunotherapy resistance. Dicer1 inactivation in TAMs (D^KO) prompts their immunostimulatory activation, enabling effective immunotherapy in mouse cancer models. Single-cell RNA sequencing (scRNA-seq) analysis revealed interferon-γ (IFNγ)-dependent immunostimulatory programming of the tumor microenvironment in D^KO mice. In tumors of wild-type mice and patients with cancer, dynamic inferences on macrophage ontogeny by pseudotime analysis identified trajectories associated with monocyte-to-macrophage differentiation, progression into the cell cycle, and transition from immunostimulatory (M1-like) to immunosuppressive and protumoral (M2-like) states.

SUBMITTER: Duval F 

PROVIDER: S-EPMC12139442 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature