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High prevalence of Foxp3 and IL-17 in MMR-proficient colorectal carcinomas
  1. Sabine Le Gouvello
  1. Departments of Biological Immunology, France
    1. Sylvie Bastuji-Garin
    1. Public Health, France
      1. Nijez Aloulou
      1. Gastroenterology, France
        1. Hicham Mansour
        1. Biological Immunology, France
          1. Marie Theres Chaumette
          1. Pathology, France
            1. françois Berrehar
            1. Biological Immunology, France
              1. Amel Seikour
              1. Pathology, France
                1. Antoine Charachon
                1. Gastroenterology, France
                  1. Mehdi Karoui
                  1. Surgery, France
                    1. Karen Leroy
                    1. Pathology, France
                      1. Jean Pierre Farcet
                      1. Biological Immunology, France
                        1. Iradj SOBHANI (iradj.sobhani{at}hmn.aphp.fr)
                        1. Gastroenterology & Oncology CHU Henri Mondor, France

                          Abstract

                          Background & Aims: Colon cancer (CRC) harbors 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 tumors. Our aim was to characterize the intratumoral expression of markers associated with the anti-tumour immune response in 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 RT-PCR. mRNA levels were correlated with MMR status. Immunohistochemistry (IHC) including both IL17 and CD3 antibodies was used. Results: Expression of cytotoxic markers (FasL, granzyme B and perforin), inflammatory cytokines (IL-1beta, IL-6, IL-8, IL-17 and TGFbeta and a marker of regulatory T cells (Foxp3) were significantly higher in tumors than in autologous normal tissues. Adjusting for MMR status, higher tumoral expression of both Gz 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 tumoral expression of Foxp3, IL-17, IL-1beta, IL-6, and TGF-beta was associated with the MSS phenotype, and the IL-17 T/NT ratio was higher in MSS tissues than in MSI-H tissues by using either RT-PCR or IHC. Conclusions: Immune gene expression profiling in CRC displayed different patterns according to MMR status. Higher Foxp3, IL-6, TGF-beta and IL17 expressions are particular determinants in MMR-proficient CRC. They may be potential biomarkers for a new prognostic “test set” in sporadic CRCs.

                          • Foxp3
                          • IL-17
                          • IL6
                          • MSI
                          • colon cancer

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