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TGF-?1 contributes to CD8+ Treg induction through p38 MAPK signaling in ovarian cancer microenvironment.


ABSTRACT: 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-?1 in CD8+ Treg induction by the OC microenvironment. OC patients expressed high levels of TGF-?1, as did the co-culture supernatant from CD8+ T cells and SKOV3. Additionally, TGF-?1 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-?1 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-?1-neutralizing antibody. Moreover, the p38 specific inhibitor SB203580 dose-dependently blocked the TGF-?1 activated conversion of CD8+ T cells into CD8+ Tregs. These data suggested that in vitro-induction of CD8+ Tregs depended in part on TGF-?1 activation of p38 MAPK signaling. Therefore, p38 MAPK could be a therapeutic target in OC anti-tumor immunotherapy.

SUBMITTER: Wu M 

PROVIDER: S-EPMC5190116 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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TGF-β1 contributes to CD8+ Treg induction through p38 MAPK signaling in ovarian cancer microenvironment.

Wu Meng M   Chen Xian X   Lou Jianfang J   Zhang Shuping S   Zhang Xiaojie X   Huang Lei L   Sun Ruihong R   Huang Peijun P   Wang Fang F   Pan Shiyang S  

Oncotarget 20160701 28


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  ...[more]

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