Intratumoral regulatory T cells are associated with suppression of colorectal carcinoma metastasis after resection through overcoming IL-17 producing T cells

Abstract

With opposite immune activities, regulatory T cells (Tregs) and IL-17 producing T cells were accumulated in various malignant tumors and played critical roles in pathophysiologic course of these diseases. In this study, we investigated the mix-effect of the intratumoral Tregs and IL-17 producing T cells on metastasis of colorectal carcinoma (CRC) after resection. The frequency of intratumoral Tregs and IL-17A+ T cells, and the levels of FoxP3 and IL-17 mRNA were analyzed. The ratio of Tregs/IL-17A+T cells and the ratio of FoxP3 mRNA/IL-17 mRNA were calculated. The activities of matrix metalloproteases (MMPs) in tumor tissues were analyzed. Meanwhile, Tregs from patient's blood was co-cultured with human CRC cells in the presence of IL-17. MMPs protein and mRNA levels were determined after 48 or 24h incubation. We found that Tregs and IL-17A+T cells were accumulated in CRC. The ratio of Tregs/IL-17A+T cells was decreased in CRC tissues. More intratumoral Tregs and less IL-17A+T cells were associated with suppressed MMPs activities and decreased metastases score. In addition, vitro studies demonstrated that Tregs suppressed MMPs expression in the presence of IL-17. Our findings suggested the possibility that intratumoral Tregs protected against metastasis of CRC after resection through overcoming IL-17 producing T cells.

Keywords: Colorectal carcinoma; IL-17; Matrix metalloproteases; Regulatory T cells.