In:
British Journal of Pharmacology, Wiley, Vol. 177, No. 4 ( 2020-02), p. 884-897
Abstract:
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 (H 2 S), a gasotransmitter whose anti‐cancer effects are well known, to inhibit the accumulation and immunosuppressive functions of MDSCs in melanoma. Experimental Approach Effects of H 2 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 H 2 S donor, diallyl trisulfide (DATS) and analysed for content of MDSCs, dendritic cells (DCs) and T cells. Effects of H 2 S on expression of immunosuppressive genes in MDSCs and on T cell proliferation were evaluated. Key Results 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. Conclusions and Implications The H 2 S donor compound, DATS, inhibited the expansion and the suppressive functions of MDSCs, suggesting a novel role for H 2 S as a modulator of MDSCs in cancer. Therefore, H 2 S donors may provide a novel approach for enhancing the efficacy of melanoma immunotherapy. Linked Articles 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
Type of Medium:
Online Resource
ISSN:
0007-1188
,
1476-5381
Language:
English
Publisher:
Wiley
Publication Date:
2020
detail.hit.zdb_id:
2029728-2
SSG:
15,3
Permalink