ImmunoTargets and Therapy (May 2020)
Dendritic Cell-Based Therapy Using LY6E Peptide with a Putative Role Against Colorectal Cancer
Abstract
Samaneh Tokhanbigli,1,* Ali Asadirad,2,* Kaveh Baghaei,1 Andrea Piccin,3,4 Fatemeh Yarian,5 Gilda Parsamanesh,1 Seyed Mahmoud Hashemi,6 Hamid Asadzadeh Aghdaei,1 Mohammad Reza Zali7 1Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 2Department of Immunology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; 3Haematology Department, Our Lady’s Children’s Hospital, Dublin, Ireland; 4Department of Internal Medicine V, University of Innsbruck, Innsbruck, Austria; 5Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 6Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 7Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran*These authors contributed equally to this workCorrespondence: Kaveh BaghaeiResearch Institute of Gastroenterology and Liver Disease (RIGLD), Aerabi St, Yemen St, Chamran Highway, Tehran, IranTel +98 9123592868Email [email protected] PiccinHaematology Department, Our Lady’s Children’s Hospital, Dublin, IrelandTel +353 89 6082831Email [email protected]: 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.Methods: 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.Results: 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.Discussion: 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.Keywords: dendritic cell, colorectal cancer, LY6E, dendritic cell tumor-associated antigen therapy
