ILCs, the Frontliners of Immune Defense in Mouse Model of Colorectal Cancer

Abstract

Background and Objective: Innate lymphoid cells (ILCs) have been shown to play important roles in tumor immunity. We studied the frequency of three subsets of circulating ILCs in mouse models of colorectal cancer (CRC). Methods: Two mouse models of CRC were developed; including a chemically-induced model, via administration of azoxymethane/dextran sulfate sodium (AOM/DSS), and an orthotopic mouse model, using the CT-26 cell line. Based on histopathological examinations, mice were divided into 3 groups of dysplasia group (consists of chemically-induced and orthotopic induced), chemically-induced reparative change group, normal. A sham group was also considered in which mice were screened for stresses that originated from interventions and injections. Flow cytometry analysis was performed to evaluate the frequencies of ILC1, ILC2, and ILC3 in the peripheral blood of all studied mice.Results: The frequency of ILC1 was significantly higher in the chemically-induced reparative change group compared to the sham and dysplasia groups. ILC2s showed higher frequencies in the dysplasia groups than the sham and chemically-induced reparative change groups. In addition, altered composition of ILCs was observed in peripheral blood of dysplastic mice skewing toward ILC3s in the dysplasia groups compared to sham and chemically-induced reparative change groups. Conclusions: A higher frequency of ILC1 in the reparative change group suggests a potentially anti-tumorigenic role. Higher ILC2s might be in favor of differentiation from the reparative change stage to the dysplasia. In addition, it seems likely that ILC3s are participating in the primary stages of CRC development.