Journal
ONCOIMMUNOLOGY
Volume 10, Issue 1, Pages -Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/2162402X.2021.1950953
Keywords
Cancer-associated fibroblasts; hypoxia; immunosuppression; CTL
Categories
Funding
- INSERM
- French Ligue Nationale Contre Le Cancer (LNCC-Equipe Labellisee)
- French Ligue Nationale Contre Le Cancer
- taxe d'apprentissage program (Direction de la Recherche-Gustave Roussy)
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This study reveals that hypoxia increases the expression and secretion of immunosuppressive factors by melanoma-associated fibroblasts, with hypoxic CAF secretome exerting a more profound effect on T cell-mediated cytotoxicity than normoxic counterpart. The crosstalk between hypoxia and CAFs may be an important determinant in the complex immunosuppressive tumor microenvironment.
Cancer-associated fibroblasts (CAFs) and hypoxia are central players in the complex process of tumor cell-stroma interaction and are involved in the alteration of the anti-tumor immune response by impacting both cancer and immune cell populations. However, even if their independent immunomodulatory properties are now well documented, whether the interaction between these two components of the tumor microenvironment can affect CAFs ability to alter the anti-tumor immune response is still poorly defined. In this study, we provide evidence that hypoxia increases melanoma-associated fibroblasts expression and/or secretion of several immunosuppressive factors (including TGF-beta, IL6, IL10, VEGF and PD-L1). Moreover, we demonstrate that hypoxic CAF secretome exerts a more profound effect on T cell-mediated cytotoxicity than its normoxic counterpart. Together, our data suggest that the crosstalk between hypoxia and CAFs is probably an important determinant in the complex immunosuppressive tumor microenvironment.
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