Cancer-associated fibroblasts as mediators of tissue microenvironment remodeling in cancer

Cancer-associated fibroblasts (CAFs) are a multifunctional cell population of solid tumors that substantially remodel the tumor microenvironment (TME). The combination of single-cell and spatial technologies with elegant mouse models and analysis of patient samples is enabling unprecedented advances in the characterization of CAF origins, heterogeneity, and functions within the TME. As such, the field is now evolving to delineate tissue-specific subpopulations of CAFs, their markers, and the biological context in which each subset presents with a tumor-promoting or a tumor-restraining function. In this timely review, we discuss recent advances in CAF biology in the context of emerging areas of interest in the field of anticancer therapy: immunotherapy, metabolism, and extracellular vesicles. We also highlight the substantial role of CAFs in modulating the immune microenvironment and the recent advances in targeting CAFs for cancer treatment.