Cancer-associated fibroblasts: Versatile mediators in remodeling the tumor microenvironment

Current cancer therapeutic strategies are generally not sufficient to eradicate malignancy, as cancer stroma cells contribute to tumor evasion and therapeutic resistance. Cancer-associated fibroblasts (CAFs) constitute a largely heterogeneous type of stromal cell population and are important components of the tumor microenvironment (TME). CAFs are the most abundant stromal cell type and are actively involved in tumor progression through complex mechanisms involving effects on other cell types. Research conducted in recent years has emphasized an emerging function of CAFs in the remodeling of the TME that promotes tumor progression with effects on response to treatment by various molecular mechanisms. A comprehensive mechanism of tumor-promoting activities of CAFs could facilitate the development of novel diagnostic and therapeutic approaches. In this review, the biological characterization of CAFs and the mechanisms of their effects on TME remodeling are summarized. Furthermore, we also highlight currently available therapeutic strategies targeting CAF in the context of optimizing the success of immunotherapies and briefly discuss possible future perspectives and challenges related to CAF studies.