Tumor-associated macrophages restrict CD8⁺ T cell function through collagen deposition and metabolic reprogramming of the breast cancer microenvironment.

ABSTRACT: Tumor progression is accompanied by fibrosis, a condition of excessive extracellular matrix accumulation, which is associated with diminished antitumor immune infiltration. Here we demonstrate that tumor-associated macrophages (TAMs) respond to the stiffened fibrotic tumor microenvironment (TME) by initiating a collagen biosynthesis program directed by transforming growth factor-β. A collateral effect of this programming is an untenable metabolic milieu for productive CD8⁺ T cell antitumor responses, as collagen-synthesizing macrophages consume environmental arginine, synthesize proline and secrete ornithine that compromises CD8⁺ T cell function in female breast cancer. Thus, a stiff and fibrotic TME may impede antitumor immunity not only by direct physical exclusion

SUBMITTER: Tharp KM 

PROVIDER: S-EPMC12204312 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature