Modulation of the antitumor immune response by cancer-associated fibroblasts: mechanisms and targeting strategies to hamper their immunosuppressive functions

Cancer-associated fibroblasts (CAFs) are highly heterogeneous players that shape the tumor microenvironment and influence tumor progression, metastasis formation, and response to conventional therapies. During the past years, some CAFs subsets have also been involved in the modulation of immune cell functions, affecting the efficacy of both innate and adaptive anti-tumor immune responses. Consequently, the implication of these stromal cells in the response to immunotherapeutic strategies raised major concerns. In this review, current knowledge of CAFs origins and heterogeneity in the tumor stroma, as well as their effects on several immune cell populations that explain their immunosuppressive capabilities are summarized. The current development of therapeutic strategies for targeting this population and their implication in the field of cancer immunotherapy is also highlighted.