Follicular regulatory T cells infiltrated the ovarian carcinoma and resulted in CD8 T cell dysfunction dependent on IL-10 pathway |
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| Institution: | 1. Traditional and Complementary Medicine Research Center (TCMRC), Arak University of Medical Sciences, Arak, Iran;2. Department of Immunology, School of Medicine, Arak University of Medical Sciences, Arak, Iran;3. Molecular and Medicine Research Center, Arak University of Medical Sciences, Arak, Iran;4. General Practitioner, Arak, Iran;1. Institute of Blood Transfusion, Shanghai Blood Center, Shanghai 200051, China;2. School of Life Science, Shanghai University, Shanghai 200444, China;3. Department of Biochemistry and Molecular Medicine, The George Washington University School of Medicine and Health Sciences, Washington, DC 20037, USA;1. Department of Medicine, Mount Sinai West and Mount Sinai Morningside, New York, NY, USA;2. Icahn School of Medicine at Mount Sinai, New York, NY, USA;3. Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland;4. Comprehensive Cancer Center Zurich, Zurich, Switzerland |
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| Abstract: | A high Treg/CD8 T cell ratio in ovarian carcinoma was negatively associated with the prognosis of the patients. The human follicular regulatory T (Tfr) cells are a newly characterized subset of Treg cells with features of both follicular helper T (Tfh) cells (CXCR5+) and canonical Treg cells (CD25+Foxp3+). The role of Tfr cells in ovarian cancer is yet unclear. We found that in peripheral blood, the ovarian cancer patients presented significantly higher levels of both CD4+CD25+CD127?CXCR5+ T cells and CD4+CD25+CD127?CXCR5+Foxp3+ T cells than the healthy controls. In resected tumor samples, Tfr cells represented a much greater percentage of lymphocytes than in peripheral blood. Interestingly, the circulating Tfr cells from ovarian cancer patients presented significantly higher TGFB1 and IL10 expression than their counterparts in healthy controls directly ex vivo, and significantly higher IL10 after stimulation. The tumor-infiltrating Tfr cells presented further upregulated expression of TGFB1 and IL10. In addition, the levels of TGFB1 and IL10 expression by Tfr cells negatively associated with the expression of IFNG in tumor-infiltrating CD8 T cells. In an in vitro CD8 T cell/Tfr cell coculture system, we found that Tfr cells could significantly suppress the activation of CD8 T cells, in a manner that was dependent on IL-10 and probably on TGF-β. Overall, our study found that Tfr cells could suppress CD8 T cells, and in ovarian cancer patients, the Tfr cells were increased in both frequency and function. |
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