Hepatic carcinoma-associated fibroblasts induce IDO-producing regulatory dendritic cells through IL-6-mediated STAT3 activation

Although carcinoma-associated fibroblasts (CAFs) in tumor microenvironments have a critical role in immune cell modulation, their effects on the generation of regulatory dendritic cells (DCs) are still unclear. In this study, we initially show that CAFs derived from hepatocellular carcinoma (HCC) tu...

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Vydáno v:Oncogenesis (New York, NY) Ročník 5; číslo 2; s. e198
Hlavní autoři: Cheng, J-t, Deng, Y-n, Yi, H-m, Wang, G-y, Fu, B-s, Chen, W-j, Liu, W, Tai, Y, Peng, Y-w, Zhang, Q
Médium: Journal Article
Jazyk:angličtina
Vydáno: London Nature Publishing Group UK 22.02.2016
Nature Publishing Group
Témata:
13/21
13/31
631/67/580/1884
Apoptosis
Cell Biology
Human Genetics
Internal Medicine
Medicine
Medicine & Public Health
Oncology
Original
original-article
ISSN:2157-9024, 2157-9024
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Shrnutí:Although carcinoma-associated fibroblasts (CAFs) in tumor microenvironments have a critical role in immune cell modulation, their effects on the generation of regulatory dendritic cells (DCs) are still unclear. In this study, we initially show that CAFs derived from hepatocellular carcinoma (HCC) tumors facilitate the generation of regulatory DCs, which are characterized by low expression of costimulatory molecules, high suppressive cytokines production and enhanced regulation of immune responses, including T-cell proliferation impairment and promotion of regulatory T-cell (Treg) expansion via indoleamine 2,3-dioxygenase (IDO) upregulation. Our findings also indicate that STAT3 activation in DCs, as mediated by CAF-derived interleukin (IL)-6, is essential to IDO production. Moreover, IDO inhibitor, STAT3 and IL-6 blocking antibodies can reverse this hepatic CAF-DC regulatory function. Therefore, our results provide new insights into the mechanisms by which CAFs induce tumor immune escape as well as a novel cancer immunotherapeutic approach (for example, targeting CAFs, IDO or IL-6).
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These authors contributed equally to this work.
The two authors share senior authorship.
ISSN:2157-9024
2157-9024
DOI:10.1038/oncsis.2016.7