Dendritic Cell-Based Therapy Using LY6E Peptide with a Putative Role Against Colorectal Cancer

Albeit early stage gastrointestinal (GI) carcinomas have a good prognosis if treated with surgery, diagnosis is often confirmed at a late stage and efficacious drugs are lacking. Recent progress in immune-based therapies has focused on dendritic cells (DCs), aiming to elicit tumor-specific responses by inducing immunological memory. Our previous microarray study indicated that a biomarker, termed lymphocyte antigen-6E (LY6E), is commonly overexpressed in two potentially lethal GI cancers: those of colon and stomach. In this study, we examined the antigenic potency of LY6E in stimulating DCs.

Following isolation, differentiation, and maturation of mononuclear cells, DCs were pulsed with LY6E peptide, a protein related to major histocompatibility complex (MHC) class I/II. Subsequently, DCs were co-cultured with mouse splenocytes to assess antigen-specific T-cell proliferation. Elucidated cytotoxic T-lymphocyte responses were assessed using subcutaneous colorectal murine tumor models.

Our in vitro results suggest that DCs loaded with LY6E peptide antigen are capable of stimulating and inducing proliferation of murine T-cells. Furthermore, our in vivo results demonstrate that LY6E peptide has a substantial impact on provoking immune responses against induced colon cancer in mice.

In conclusion, based on the overexpression of LY6E in colorectal, gastric, and pancreatic cancers, the role of this peptide should be further investigated with a goal of developing new therapies for these challenging diseases.