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Cheng JT, Deng YN, Yi HM, et al. Hepatic carcinoma-associated fibroblasts induce IDO-producing regulatory dendritic cells through IL-6-mediated STAT3 activation. Oncogenesis. 2016;5:e198doi: 10.1038/oncsis.2016.7.
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. (2016). Hepatic carcinoma-associated fibroblasts induce IDO-producing regulatory dendritic cells through IL-6-mediated STAT3 activation. Oncogenesis, 5e198. https://doi.org/10.1038/oncsis.2016.7
Cheng, J-T, et al. "Hepatic carcinoma-associated fibroblasts induce IDO-producing regulatory dendritic cells through IL-6-mediated STAT3 activation." Oncogenesis vol. 5 (2016): e198. doi: https://doi.org/10.1038/oncsis.2016.7
Cheng JT, Deng YN, Yi HM, Wang GY, Fu BS, Chen WJ, Liu W, Tai Y, Peng YW, Zhang Q. Hepatic carcinoma-associated fibroblasts induce IDO-producing regulatory dendritic cells through IL-6-mediated STAT3 activation. Oncogenesis. 2016 Feb 22;5:e198. doi: 10.1038/oncsis.2016.7. PMID: 26900950; PMCID: PMC5154347.
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Oncogenesis. 2016 Feb 22;5:e198. doi: 10.1038/oncsis.2016.7.

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

Oncogenesis

J-T Cheng, Y-N Deng, H-M Yi, G-Y Wang, B-S Fu, W-J Chen, W Liu, Y Tai, Y-W Peng, Q Zhang

Affiliations

  1. Cell-gene Therapy Translational Medicine Research Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
  2. Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou, China.
  3. Department of Hepatic Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

PMID: 26900950 PMCID: PMC5154347 DOI: 10.1038/oncsis.2016.7

Abstract

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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