Association of IL-12Bpro polymorphism with tumor-infiltrating dendritic cells in colorectal cancer

Purpose: Chronic inflammation is a key component in the development and progression of colorectal cancer (CRC). A notable hallmark of the inflammation process is the release of pro-inflammatory cytokines by infiltrating cells of the immune system. Defects in dendritic cells (DCs) recruitment, maturation and cytokine release are a hallmark of the CRC strategy to escape immune surveillance.The purpose of our study was to evaluate the possible role of IL-12B polymorphism in the promoter region of the IL-12B gene (rs17860508) as a genetic factor contributing to the risk for CRC development. Additionally, we aimed to evaluate the influence of this polymorphism on DCs infiltration in tumor microenvironment. Methods: IL-12Bpro polymorphism was genotyped by Amplification Refractory Mutation System-Polymerase Chain Reaction (ARMS-PCR). Immunohistochemistry was performed for DCs infiltration. Results: Statistically significant correlation between the expression of S100 and CD1a DCs and the 11-genotype of the studied polymorphism was found. No statistically significant difference in genotype distribution between cases and controls was observed (p=0.163). Analysis of the overall survival (OS) of genotyped patients revealed a tendency among the carriers of the 22-genotype to have shorter survival of 36 months versus the 11- and 12-cariers- 61 months (log rank, p=0.117). Conclusions: The IL-12Bpro polymorphism does not constitute a risk factor for CRC development. However, geno-type-11 might have a complex role in the recruitment and maturation of DCs in tumor microenvironment.