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.