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Modulation of the functions of myeloid-derived suppressor cells : a new strategy of hydrogen sulfide anti-cancer effects.
- Source :
- British Journal of Pharmacology; 2/15/2020, Vol. 177 Issue 4, p884-897, 14p, 1 Black and White Photograph, 5 Graphs
- Publication Year :
- 2020
-
Abstract
- <bold>Background and Purpose: </bold>Myeloid-derived suppressor cells (MDSCs) represent a major obstacle to cancer treatment, as they negatively regulate anti-tumour immunity through the suppression of tumour-specific T lymphocytes. Thus, the efficacy of immunotherapies may be improved by targeting MDSCs. In this study, we assessed the ability of hydrogen sulfide (H2 S), a gasotransmitter whose anti-cancer effects are well known, to inhibit the accumulation and immunosuppressive functions of MDSCs in melanoma.<bold>Experimental Approach: </bold>Effects of H2 S on the host immune response to cancer were evaluated using an in vivo syngeneic model of murine melanoma. B16F10-melanoma-bearing mice were treated with the H2 S donor, diallyl trisulfide (DATS) and analysed for content of MDSCs, dendritic cells (DCs) and T cells. Effects of H2 S on expression of immunosuppressive genes in MDSCs and on T cell proliferation were evaluated.<bold>Key Results: </bold>In melanoma-bearing mice, DATS inhibited tumour growth, and this effect was associated with a reduction in the frequency of MDSCs in the spleen, in the blood as well as in the tumour micro-environment. In addition, we found that CD8+ T cells and DCs were increased. Furthermore, DATS reduced the immuno-suppressive activity of MDSCs, restoring T cell proliferation.<bold>Conclusions and Implications: </bold>The H2 S donor compound, DATS, inhibited the expansion and the suppressive functions of MDSCs, suggesting a novel role for H2 S as a modulator of MDSCs in cancer. Therefore, H2 S donors may provide a novel approach for enhancing the efficacy of melanoma immunotherapy.<bold>Linked Articles: </bold>This article is part of a themed section on Hydrogen Sulfide in Biology & Medicine. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.4/issuetoc. [ABSTRACT FROM AUTHOR]
- Subjects :
- SUPPRESSOR cells
HYDROGEN sulfide
T cells
DENDRITIC cells
IMMUNE response
BIOLOGY
Subjects
Details
- Language :
- English
- ISSN :
- 00071188
- Volume :
- 177
- Issue :
- 4
- Database :
- Complementary Index
- Journal :
- British Journal of Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 141781093
- Full Text :
- https://doi.org/10.1111/bph.14824