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Fibroblasts Influence the Efficacy, Resistance, and Future Use of Vaccines and Immunotherapy in Cancer Treatment
Vaccines (Basel). 2021 Jun 10;9(6)
PMID: 34200702    PMCID: PMC8230410    URL: https://www.ncbi.nlm.nih.gov/pubmed/34200702
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Tumors are composed of not only epithelial cells but also many other cell types that contribute to the tumor microenvironment (TME). Within this space, cancer-associated fibroblasts (CAFs) are a prominent cell type, and these cells are connected to an increase in tumor progression as well as alteration of the immune landscape present in and around the tumor. This is accomplished in part by their ability to alter the presence of both innate and adaptive immune cells as well as the release of various chemokines and cytokines, together leading to a more immunosuppressive TME. Furthermore, new research implicates CAFs as players in immunotherapy response in many different tumor types, typically by blunting their efficacy. Fibroblast activation protein (FAP) and transforming growth factor β (TGF-β), two major CAF proteins, are associated with the outcome of different immunotherapies and, additionally, have become new targets themselves for immune-based strategies directed at CAFs. This review will focus on CAFs and how they alter the immune landscape within tumors, how this affects response to current immunotherapy treatments, and how immune-based treatments are currently being harnessed to target the CAF population itself.
2076-393x Sliker, Bailee H Orcid: 0000-0002-4686-4221 Campbell, Paul M Orcid: 0000-0002-3345-5007 NCI 5T32CA009035-43/CA/NCI NIH HHS/United States P30 CA006927/CA/NCI NIH HHS/United States Journal Article Review Vaccines (Basel). 2021 Jun 10;9(6):634. doi: 10.3390/vaccines9060634.