Abstract 784: Prevalence, phenotype and prognostic significance of IL-17-producing cells infiltratinghuman colorectal cancers

Abstract

Abstract Background: Lymphocytic infiltration is known to be associated with a favourable prognosis in human colorectal cancer (CRC). In particular, the presence of CD8+ T cells and, unexpectedly, of Foxp3+ regulatory T cells, has been found to be associated with improved patient survival. Recent evidence suggests that IL-17 and T helper (Th) 17 cells might also have an impact on anti-tumour immune responses. We have investigated prevalence, phenotype and prognostic significance of IL-17-producing cells in human CRC. Material and Methods: IL-17 expression was evaluated by immunohistochemistry on a tissue micro-array (TMA) including 1420 cases of primary CRC with full clinico-pathological data. Furthermore, gene expression levels were assessed on CRC tissues by quantitative PCR. Finally, in order to characterize the phenotype of IL-17-positive cells, expression of IL-17, in combination with that of specific surface molecules, was analyzed on freshly excised CRC specimens by flow cytometry. Results: Frequencies of IL-17-producing cells, as well as IL-17 gene expression levels were significantly increased in tumour tissues as compared to autologous normal mucosa. IL-17-producing cells isolated from clinical specimens were exclusively comprised within the lymphocyte population and expressed CD4, but not CD8, and surprisingly, Foxp3 molecules. Accordingly, mRNA levels of genes encoding for cytokines favouring IL-17 acquisition by Foxp3+ T cells, including IL-6, IL-1beta, TGF-beta and IL-23, were found more elevated in CRC tissues as comparing to corresponding healthy mucosa. High infiltration by IL-17 producing cells significantly correlated with low T and N stages, and, most importantly, with prolonged survival time in mismatch repair (MMR)- proficient, but not-deficient CRC. Moreover, the simultaneous CRC-infiltration by IL-17+ and Foxp3+ cells was significantly associated with improved survival in both MMR-proficient and -deficient tumours. Conclusions: Our data suggest that IL-17 produced by tumour-infiltrating either CD4+ or Foxp3+ cells may promote a benign clinical outcome in CRC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 784. doi:10.1158/1538-7445.AM2011-784