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Modulation of the functions of myeloid-derived suppressor cells : a new strategy of hydrogen sulfide anti-cancer effects.

髓源性抑制细胞功能的调节: 硫化氢抗癌作用的新策略。

  • 影响因子:6.12
  • DOI:10.1111/bph.14824
  • 作者列表:"De Cicco P","Ercolano G","Rubino V","Terrazzano G","Ruggiero G","Cirino G","Ianaro A
  • 发表时间:2020-02-01
Abstract

BACKGROUND AND PURPOSE: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. EXPERIMENTAL APPROACH: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. 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 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. 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.

摘要

背景和目的: 髓源性抑制细胞 (MDSCs) 是癌症治疗的主要障碍,因为它们通过抑制肿瘤特异性 T 淋巴细胞负调节抗肿瘤免疫。因此,免疫疗法的疗效可以通过靶向 MDSCs 来改善。在这项研究中,我们评估了硫化氢 (H2 S) 的能力,这是一种众所周知的 gasotransmitter,其抗癌作用抑制 MDSCs 在黑色素瘤中的积累和免疫抑制功能。 实验方法: 使用小鼠黑色素瘤的体内同基因模型评价 H2 S 对宿主对癌症免疫应答的影响。用 H2 S 供体二烯丙基三硫 (DATS) 处理 B16F10-melanoma-bearing 小鼠,分析 MDSCs 、树突状细胞 (DCs) 和 T 细胞的含量。评价 H2 S 对 MDSCs 免疫抑制基因表达和 T 细胞增殖的影响。 关键结果: 在荷黑色素瘤小鼠中,DATS 抑制肿瘤生长,这种作用与脾脏中 MDSCs 频率的降低相关, 在血液以及肿瘤微环境中。此外,我们发现 CD8 + T 细胞和 DCs 增加。此外,DATS 降低了 MDSCs 的免疫抑制活性,恢复了 T 细胞增殖。 结论和意义: H2 S 供体化合物 DATS 抑制 MDSCs 的扩增和抑制功能,提示 H2 S 作为 MDSCs 的调节剂在癌症中的新作用。因此,H2 S 供体可能为增强黑色素瘤免疫治疗的疗效提供一种新的方法。 链接文章: 本文是生物与医学中硫化氢主题部分的一部分。要查看本节中的其他文章,请访问 http://onlinelibrary.wiley.com/doi/ 10.1111/bph.v177.4/issuetoc。

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