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TGF-β1 contributes to CD8(+) Treg induction through p38 MAPK signaling in ovarian cancer microenvironment
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 micro...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5190116/ https://www.ncbi.nlm.nih.gov/pubmed/27322208 http://dx.doi.org/10.18632/oncotarget.10003 |
Sumario: | 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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