Interleukin-17 inhibits the growth of oral squamous cell carcinoma by promoting the differentiation of T helper 17 cells

Abstract

Background: The infiltration of T helper 17 (Th17) cells has been reported in multiple solid tumors. Recent studies implicated that Th17 cells played an inhibitory role in the tumor growth. However, if Th17 cells infiltrated and played a role in oral squamous cell carcinoma (OSCC) remained unknown. Methods: Fluorescence activated cell sorting (FACS) was performed to confirm the increase of Th17 cells in the peripheral blood and the infiltration in tumor samples from OSCC patients. To mimicking the effect of Th17 cells on OSCC growth, an OSCC line stably expressing human interleukin-17A (IL-17A) was established. Human-PBL-SCID-beige mice were employed as the hosts for the implantation of OSCC/IL-17A cells. Quantitative PCR, ELISA and Western blotting were performed to analyze Th17 differentiation and function in the implanted tumors. Results: The percentage of Th17 cells increased significantly in both the peripheral blood and the tumor tissues from OSCC patients. Expression of IL-17A promoted the differentiation of Th17 cells and suppressed the growth of implanted OSCC tumors. The transcription as well as the protein levels of IL-6 and granzyme B in the implanted OSCC cells was remarkably elevated by IL-17A expression. Conclusions: The increased infiltration of Th17 cells was suggested to result in a therapeutic effect on OSCC as Th17 cells did in other tumors. IL-17 could promote the differentiation of Th17 cells by increasing IL-6 expression. The inhibitory effect of Th17 cells on OSCC growth was associated with their increased cytotoxic activity.