Background and Aim: One of the most effective approaches for cancertreating is the excitation of the immune system against tumor antigens.One of the strategies to stimulate T cell effectors and memory immuneresponse in cancer patients is to develop dendritic cell based vaccines.Microarray study indicated,
LY6E is a common over expressed biomarkerin three GI cancers, colon, gastric, and pancreatic. The current researchpurpose is in vivo study of investigation the effectiveness of adoptingdendritic cells loaded with designed
LY6E peptide antigen stimulating theMHC class I and II at the same time.Methods:
LY6E was chosen according the differential gene expressionanalysis. In the next step, Immune Epitope Database and AnalysisResource (IEDB) was used as a prediction tool for MHC class I and class IIbinding site and design of epitopes. After that mononuclear cells extractedfrom murine bone marrow were cultured in conventional cytokines. Onday 7, cells were harvested and pulsed with peptide and subsequently,they were utilized for the maturation stage with LPS. DC phenotypesand characteristic were approved by flow cytometry (MHC Class II,CD80, CD40, CD14, and CD11c). Murine CT26 cell line were injectedsubcutaneously into Balb/c mice to create tumor and matured DCs pulsedwith peptides were injected into mice. 17 days after injection, mice weresacrificed and samples were collected. Proliferation, stimulation assays,Flow cytometry, and pathology detection were carried out to confirm theefficiency of
LY6E peptide.Results: According to cytotoxicity assay (annexin/PI) extractedspelenocytes had a necrotic effect on CT26 as a cancer cell line. Regardingto tumor size, out of five treated mice, two of them showed significantamelioration. Flow cytometry analysis as another assessment, identifiedthe proliferation of CD8 positive cells as cytotoxic T lymphocytes inthe treated group. Following this, pathology samples indicated the G2grade in treated group where the untreated group had G3 and G4 gradeaccording to the TNM staging system.Conclusion: Identification and development of common tumor antigensprovide the possibility of immediate availability of DC vaccine. Theseanti-genes can provide more populations of cancer patients with availabletreatments. Finding a key player among the gastrointestinal cancers wasthe main concern of this study, therefore, by immunoinformatic approach;LY6E was detected as a core actor in three lethal GI malignancies (colon,Gastric, and pancreatic cancers). Our in vivo study characterized
LY6E asa promising therapeutic candidate in GI cancers.