High prevalence of Foxp3 and IL17 in MMR-proficient colorectal carcinomas

Department of Gastroenterology, Hôpital Henri Mondor, 51 Av. du Maréchal de Lattre de Tassigny, 94010 Créteil, France.
Gut (Impact Factor: 14.66). 07/2008; 57(6). DOI: 10.1136/gut.2007.123794
Source: PubMed


BACKGROUND AND AIMS: Colorectal cancer (CRC) harbours different types of DNA alterations, including microsatellite instability (MSI). Cancers with high levels of MSI (MSI-H) are considered to have a good prognosis, probably related to lymphocyte infiltration within tumours. The aim of the present study was to characterise the intratumoural expression of markers associated with the antitumour immune response in mismatch repair (MMR)-proficient (MSS) colon cancers. METHODS: Ninety human colon cancers (T) and autologous normal colon mucosa (NT) were quantified for the expression of 15 markers of the immune response with quantitiative reverse transcription-PCR (qRT-PCR). mRNA expression levels were correlated with MMR status. Immunohistochemistry (IHC) was performed using both interleukin 17 (IL17) and CD3 antibodies. RESULTS: Expression of cytotoxic markers (FasL, granzyme B and perforin), inflammatory cytokines (IL1beta, IL6, IL8, IL17 and transforming growth factor beta (TGFbeta)) and a marker of regulatory T cells (forkhead box P3 (Foxp3)) was significantly higher in tumours than in autologous normal tissues. Adjusting for MMR status, higher tumoural expression of both granzyme B and perforin was associated with the MSI-H phenotype, and the perforin T/NT ratio was higher in MSI-H tissues than in MSS tissues. Higher tumoural expression of Foxp3, IL17, IL1beta, IL6 and TGFbeta was associated with the MSS phenotype, and the IL17 T/NT ratio was higher in MSS tissues than in MSI-H tissues as assessed by both qRT-PCR and IHC. CONCLUSIONS: Immune gene expression profiling in CRC displayed different patterns according to MMR status. Higher Foxp3, IL6, TGFbeta and IL17 expression is a particular determinant in MMR-proficient CRC. These may be potential biomarkers for a new prognostic "test set" in sporadic CRCs.

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Available from: Hicham Mansour, Oct 26, 2014
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    • "It may be important in tumor cell growth and may contribute to the aggressiveness of human tumors [24]. Recently, accumulating evidence has shown that IL-17-positive cells are frequently present in multiple cancers, including prostate cancer [25], colorectal cancer [26], hepatocellular carcinoma [27], breast cancer [28], ovarian cancer [20] and non-small-cell lung cancer [29]. Researchers in some studies have reported that IL-17 cell expression in MPE is elevated [15,23]. "
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    European journal of medical research 05/2014; 19(1):23. DOI:10.1186/2047-783X-19-23 · 1.50 Impact Factor
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    • "IL-17 expression is elevated in several human tumors, such as ovarian cancer, cervical cancer, breast cancer, hepatocellular carcinoma, esophageal cancer, gastric cancer, and CRC [28–34]. But the underlying mechanism of IL-17 in tumor initiation and progression is not completely clear yet. "
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    Clinical and Developmental Immunology 12/2013; 2013(1):436307. DOI:10.1155/2013/436307 · 2.93 Impact Factor
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    • "[48] Inhibition of IL-6, IL-11 or Stat3 signaling can suppress the development of inflammation-associated CRC, with IL-11-Stat3 signaling playing a more prominent role than IL-6 in colonic tumorigenesis.[36], [37], [49] In the present study, IL-6, IL-11 and TNF mRNA expression were increased in colonic tumors in Iron/DSS and Control/DSS mice (Fig. 6A,C,D) consistent with other reports.[50]–[52] Dietary iron increased the number and size of DSS-induced colonic tumors and enhanced intratumoral IL-6, and possibly IL-11, expression (Fig. 6C,D) suggesting that iron promotes colonic tumorigenesis via the Stat3 signaling pathway. "
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    PLoS ONE 11/2013; 8(11):e78850. DOI:10.1371/journal.pone.0078850 · 3.23 Impact Factor
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