Fibroblasts Influence the Efficacy, Resistance, and Future Use of Vaccines and Immunotherapy in Cancer Treatment
Open Access
- 10 June 2021
- Vol. 9 (6), 634
- https://doi.org/10.3390/vaccines9060634
Abstract
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.Funding Information
- National Cancer Institute (NCI 5T32CA009035-43, P30 CA006927)
This publication has 182 references indexed in Scilit:
- Biomechanical Remodeling of the Microenvironment by Stromal Caveolin-1 Favors Tumor Invasion and MetastasisCell, 2011
- Sipuleucel-T Immunotherapy for Castration-Resistant Prostate CancerThe New England Journal of Medicine, 2010
- Chemokines and chemokine receptors: new insights into cancer-related inflammationTrends in Molecular Medicine, 2010
- T Cells and Stromal Fibroblasts in Human Tumor Microenvironments Represent Potential Therapeutic TargetsCancer Microenvironment, 2010
- Cancer-Associated Fibroblasts Are Activated in Incipient Neoplasia to Orchestrate Tumor-Promoting Inflammation in an NF-κB-Dependent MannerCancer Cell, 2010
- Opposing Effects of TGF-β and IL-15 Cytokines Control the Number of Short-Lived Effector CD8+ T CellsImmunity, 2009
- Myeloid-derived suppressor cells as regulators of the immune systemNature Reviews Immunology, 2009
- PD-1 Ligand Expression by Human Colonic Myofibroblasts/Fibroblasts Regulates CD4+ T-Cell ActivityGastroenterology, 2008
- Stromal fibroblasts in cancer initiation and progressionNature, 2004
- Production of vascular endothelial growth factor by human tumors inhibits the functional maturation of dendritic cellsNature Medicine, 1996