TGF-β1 contributes to CD8+ Treg induction through p38 MAPK signaling in ovarian cancer microenvironment
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Meng Wu1,2, Xian Chen1,2, Jianfang Lou1,2, Shuping Zhang3, Xiaojie Zhang1,2, Lei Huang1,2, Ruihong Sun1,2, Peijun Huang1,2, Fang Wang1,2, Shiyang Pan1,2
1Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, 210029, Nanjing, China
2National Key Clinical Department of Laboratory Medicine, 210029, Nanjing, China
3Department of Laboratory Medicine, The Affiliated Children Hospital, Nanjing Medical University, 210029, Nanjing, China
Fang Wang, email: firstname.lastname@example.org
Shiyang Pan, email: email@example.com
Keywords: TGF-β1, p38 MAPK, CD8+ Treg, ovarian cancer
Received: November 11, 2015 Accepted: May 29, 2016 Published: June 14, 2016
CD8+ regulatory T cells (Tregs) contribute to cancer progression and immune evasion. We previously reported that CD8+ Tregs could be induced in vitro by co-culture of CD8+ T cells with the OC cell lines SKOV3/A2780. Here, we described the role of TGF-β1 in CD8+ Treg induction by the OC microenvironment. OC patients expressed high levels of TGF-β1, as did the co-culture supernatant from CD8+ T cells and SKOV3. Additionally, TGF-β1 levels were positively correlated with CD8+ Treg percentages in OC. Neutralization experiments, cytokine studies and proliferation assays revealed that the in vitro-induced CD8+Tregs depended at least partially on up-regulated expression of TGF-β1 to exert their suppressive function. CD8+ T cells cultured with SKOV3 exhibited marked activation of p38 MAPK than CD8+ T cells cultured alone, which could be inhibited by TGF-β1-neutralizing antibody. Moreover, the p38 specific inhibitor SB203580 dose-dependently blocked the TGF-β1 activated conversion of CD8+ T cells into CD8+ Tregs. These data suggested that in vitro-induction of CD8+ Tregs depended in part on TGF-β1 activation of p38 MAPK signaling. Therefore, p38 MAPK could be a therapeutic target in OC anti-tumor immunotherapy.
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