Antigenic Potency of LY6E in Stimulating Dendritic Cells to Elicit Tumor-Specific Responses Against Human Colorectal and
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Antigenic Potency of LY6E in Stimulating Dendritic Cells to Elicit Tumor‑Specific Responses Against Human Colorectal and Gastric Cancer Cell Lines Samaneh Tokhanbigli1 · Gilda Parsamanesh1 · Kaveh Baghaei1,5 · Fatemeh Yarian2 · Ali Asadirad3 · Seyed Mahmoud Hashemi4 · Bahareh Mohebbi1 · Hamid Asadzadeh Aghdaei1 · Mohammad Reza Zali5 Accepted: 16 November 2020 © Springer Nature B.V. 2020
Abstract Early-stage gastrointestinal (GI) carcinomas are amenable malignancies, however, due to late diagnosis or lack of proper medication, alternative treatment necessitates new approaches such as dendritic cell (DC) therapy. Our previous microarray study indicated Lymphocyte antigen-6 (LY6E) as a commonly overexpressed biomarker in three lethal GI cancers, colon, gastric, and pancreatic. Therefore, we examined the antigenic potency of LY6E in stimulating DCs to elicit tumor-specific responses against human colorectal cancer (CRC) and gastric cancer (GC) cell lines HT-29 and AGS, respectively. LY6E peptide-pulsed DCs stimulated lymphocytes up to 55.9% in comparison with mature DCs (48.3%). Also, flow cytometry analysis of lymphocyte proliferation illustrated that the populations C D4+ and CD8+ were increased after treating by peptide-pulsed DCs (62.9% and 48.7% respectively). Furthermore, the cytotoxicity assay demonstrated that the 40:1 ratio of stimulated lymphocytes on AGS and HT29 cell lines was 65.1% and 66.2%, respectively. The research exposed that LY6E loaded DCs had substantial impact stimulation, proliferation, and lineage differentiation of lymphocytes. Besides, co-cultured of primed lymphocytes with AGS and HT29 cell lines exhibited cytotoxic activity. These data suggest LY6E as a potential candidate in developing DC therapy against CRC and AGS. Keywords Immune cell therapy · Gastrointestinal cancers · LY6E peptide · Dendritic cells tumor-associated antigen therapy
Samaneh Tokhanbigli and Gilda Parsamanesh contributed equally to this work. * Kaveh Baghaei [email protected] 1
Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
2
Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
3
Department of Immunology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
4
Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
5
Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Abbreviations APC Antigen-presenting cell BSA Bovine serum albumin CFSE Carboxy fluorescein diacetate succinimidyl ester CEA Carcinoembryonic antigen CRC Colorectal cancer CTL Cytotoxic T lymphocytes CTLA4 Cytotoxic T-lymphocyte-associated protein 4 DC Dendritic cell DMSO Dimethyl sulfox
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