Th17, synchronically increased with Treg and Breg, promoted by tumor cells via cell-contact in primary hepatic carcinoma

Abstract

Documented reports about Th17 cells revealed that Th17 play a critical role in inflammation and autoimmunity diseases. However, the role of Th17 in cancer remains contradictory. The interplay between Th17 and tumor cells in the tumor microenvironment of PHC needs to be further explored and the relationship between Th17, Tregs and Bregs has not been completely defined. In this study, numerous experiments were undertaken to elucidate the interaction of Th17 and Treg/Breg cells involved in PHC. Our work demonstrated that an increased Th17 were detected in the peripheral circulation and in tumor tissues in PHC patients. In addition, increases in peripheral blood Th17 corresponded with TNM stage progression. Besides, further studies indicated that Th17 cells were promoted by tumor cells in the PHC tumor microenvironment through both contact-dependent and contact-independent mechanisms, but cell-contact played the major important role in promoting the production and proliferation of Th17. When isolated CD4⁺CD25⁺ CD127^low Tregs and CD4⁺CD25^-CD127⁺ non-Tregs were cultured with autologous tumor cells, it implicated that the phenotype of Th17 and Tregs was modified by tumor cells in the tumor microenvironment. Beside this, Th17 cells were also found to correlate positively with CD4⁺FoxP3⁺Tregs and CD19⁺CD5⁺CD1d^hi Bregs in PHC. Notably, Th17 synchronically increased with Tregs and Bregs in PHC. These findings may provide new clues to reveal mechanisms of immune escape in PHC. This article is protected by copyright. All rights reserved.