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Roles of estrogens on myeloid-derived suppressor cells in cancer and autoimmune diseases

Cellular & Molecular Immunology volume 15, pages 724–726 (2018)Cite this article

As a steroid hormone, estrogen has been extensively investigated in various physiological and pathological functions and in carcinogenesis. We previously demonstrated that estrogen promotes the secretion of MICA/B through ADAM17, which helps lung cancer cells evade NKG2D-mediated immune surveillance.1 Estrogen receptor α (ERα) and ERβ are two high-affinity nuclear receptors of estrogen that promote cancer by activating multiple growth factors and inhibiting tumor-suppressor genes.2 Anti-estrogen therapy targeting the ER has been successfully used to treat ER-positive breast cancers. ER antagonists have been widely accepted in clinical practice as an effective treatment for breast tumors and a subset of ovarian cancers.3 However, for some ovarian cancer patients, anti-estrogen therapy is not suitable. Most studies have exclusively focused on ER pathways and have ignored the interaction between estrogens and other immune cells in the tumor microenvironment.

Myeloid-derived suppressor cells (MDSCs) constitute a heterogeneous group of immune cells from the myeloid lineage. MDSCs were originally described as suppressors of T cells, particularly CD8+ T cells and have been confirmed to have critical roles in diseases, such as cancers and autoimmune disorders. Regarding the relationship between estrogen and MDSCs, it has been demonstrated that estrogens can promote the development of different estrogen-insensitive tumors by mobilizing MDSCs and enhancing their inhibitory functions via ERα signaling, which is independent of the direct effects of estrogens on tumor cells.4 Estrogen signaling activates the signal transducer and activator of transcription factor 3 pathway in bone marrow myeloid precursors by enhancing Janus-activated kinase 2 and SRC activity, resulting in increased numbers of both myelomonocytic MDSCs and granulocytic MDSCs in tumor-bearing mice. A similar study showed that estrogens promote the progression of ER-negative breast cancer through the accumulation of MDSCs in the tumor microenvironment.5 The significant effects of estrogens on antitumor immunity and tumor-promoting inflammation independent of direct actions on tumor cells provide novel insight into the clinical use of anti-estrogen drugs. Accordingly, ER antagonists that specifically block ERα could be used as adjuvant therapy in ER-positive breast cancer and other malignancies. MDSC induction during immunotherapy contributes to treatment failure in many tumors. The efficiency of anti-estrogen drugs in mitigating immunotherapeutic resistance requires further confirmation. In addition, MDSCs are reported to promote tumor angiogenesis, invasion and metastasis in cases of multiple cancers. Further studies are urgently needed to clarify the effects of anti-estrogen agents on tumor metastasis and angiogenesis.

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References

  1. Ren J, Nie Y, Lv M, Shen S, Tang R, Xu Y et al. Estrogen upregulates MICA/B expression in human non-small cell lung cancer through the regulation of ADAM17. Cell Mol Immunol 2015; 12: 768–776.

    Article  CAS  Google Scholar 

  2. Krege JH, Hodgin JB, Couse JF, Enmark E, Warner M, Mahler JF et al. Generation and reproductive phenotypes of mice lacking estrogen receptor beta. Proc Natl Acad Sci USA 1998; 95: 15677–15682.

    Article  CAS  Google Scholar 

  3. Turner NC, Neven P, Loibl S, Andre F. Advances in the treatment of advanced oestrogen-receptor-positive breast cancer. Lancet 2017; 389: 2403–2414.

    Article  CAS  Google Scholar 

  4. Svoronos N, Perales-Puchalt A, Allegrezza MJ, Rutkowski MR, Payne KK, Tesone AJ et al. Tumor cell-independent estrogen signaling drives disease progression through mobilization of myeloid-derived suppressor cells. Cancer Discov 2017; 7: 72–85.

    Article  CAS  Google Scholar 

  5. Ouyang L, Chang W, Fang B, Qin J, Qu X, Cheng F. Estrogen-induced SDF-1alpha production promotes the progression of ER-negative breast cancer via the accumulation of MDSCs in the tumor microenvironment. Sci Rep 2016; 6: 39541.

    Article  CAS  Google Scholar 

  6. Wang J, Nuite M, McAlindon TE. Association of estrogen and aromatase gene polymorphisms with systemic lupus erythematosus. Lupus 2010; 19: 734–740.

    Article  CAS  Google Scholar 

  7. Ji J, Xu J, Zhao S, Liu F, Qi J, Song Y et al. Myeloid-derived suppressor cells contribute to systemic lupus erythaematosus by regulating differentiation of Th17 cells and Tregs. Clin Sci 2016; 130: 1453–1467.

    Article  CAS  Google Scholar 

  8. Dong G, You M, Fan H, Ji J, Ding L, Li P et al. 17beta-estradiol contributes to the accumulation of myeloid-derived suppressor cells in blood by promoting TNF-alpha secretion. Acta Biochim Biophys Sin (Shanghai) 2015; 47: 620–629.

    Article  CAS  Google Scholar 

  9. Weckerle CE, Mangale D, Franek BS, Kelly JA, Kumabe M, James JA et al. Large-scale analysis of tumor necrosis factor alpha levels in systemic lupus erythematosus. Arthritis Rheum 2012; 64: 2947–2952.

    Article  CAS  Google Scholar 

  10. Whitfield-Larry F, Felton J, Buse J, Su MA. Myeloid-derived suppressor cells are increased in frequency but not maximally suppressive in peripheral blood of Type 1 diabetes mellitus patients. Clin Immunol 2014; 153: 156–164.

    Article  CAS  Google Scholar 

  11. Fujii W, Ashihara E, Hirai H, Nagahara H, Kajitani N, Fujioka K et al. Myeloid-derived suppressor cells play crucial roles in the regulation of mouse collagen-induced arthritis. J Immunol 2013; 191: 1073–1081.

    Article  CAS  Google Scholar 

  12. Guo C, Hu F, Yi H, Feng Z, Li C, Shi L et al. Myeloid-derived suppressor cells have a proinflammatory role in the pathogenesis of autoimmune arthritis. Ann Rheum Dis 2016; 75: 278–285.

    Article  CAS  Google Scholar 

  13. Westendorf AM, Fleissner D, Deppenmeier S, Gruber AD, Bruder D, Hansen W et al. Autoimmune-mediated intestinal inflammation-impact and regulation of antigen-specific CD8+ T cells. Gastroenterology 2006; 131: 510–524.

    Article  CAS  Google Scholar 

  14. Yi H, Guo C, Yu X, Zuo D, Wang XY. Mouse CD11b+Gr-1+ myeloid cells can promote Th17 cell differentiation and experimental autoimmune encephalomyelitis. J Immunol 2012; 189: 4295–4304.

    Article  CAS  Google Scholar 

  15. Ioannou M, Alissafi T, Lazaridis I, Deraos G, Matsoukas J, Gravanis A et al. Crucial role of granulocytic myeloid-derived suppressor cells in the regulation of central nervous system autoimmune disease. J Immunol 2012; 188: 1136–1146.

    Article  CAS  Google Scholar 

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Acknowledgements

This work was supported by Natural Science Foundation of China (81572354 and 81772542) and Natural Science Foundation of Jiangsu Province, China (BK20161400).

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  1. The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, 210093, Nanjing, China

    Jing Ren, Yayi Hou & Tingting Wang

  2. Jiangsu Key Laboratory of Molecular Medicine, 210093, Nanjing, China

    Yayi Hou & Tingting Wang

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Ren, J., Hou, Y. & Wang, T. Roles of estrogens on myeloid-derived suppressor cells in cancer and autoimmune diseases. Cell Mol Immunol 15, 724–726 (2018). https://doi.org/10.1038/cmi.2017.129

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