<p>Dendritic Cell-Based Therapy Using LY6E Peptide with a Putative Role Against Colorectal Cancer</p>

Abstract

Introduction: 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.

Multidimension Analysis of the Prognostic Value, Immune Regulatory Function, and ceRNA Network of LY6E in Individuals with Colorectal Cancer

“…These findings suggest that LY6E plays an important role in the regulation of immune infiltrating cells in CRC. The findings of similar previously performed studies have demonstrated that the LY6E peptide had the capability to provoke an immune response [35], specifically in modulating T cell activation and proliferation [30,36,37]. Another research shows that LY6E-loaded dendritic cells did efficiently stimulate T cell subtypes, and a significantly increased proportion of Th1 cells [35].…”

“…The findings of similar previously performed studies have demonstrated that the LY6E peptide had the capability to provoke an immune response [35], specifically in modulating T cell activation and proliferation [30,36,37]. Another research shows that LY6E-loaded dendritic cells did efficiently stimulate T cell subtypes, and a significantly increased proportion of Th1 cells [35]. Thus, LY6E is an important molecule that can be used to target tumor antigens in multiple cancers.…”

Emerging Strategies of Engineering and Tracking Dendritic Cells for Cancer Immunotherapy

“…The results suggested that DCs pulsed with LY6E peptide antigen strongly matured and activated T cells. 75 Tumor lysate and tumor-derived exosomes are also used to activate DCs, and the results show that they can induce T cell activation and proliferation. 76,77 Moreover, it avoids the limitation of antigen selection and is accepted widely by patients.…”

“…Tokhanbigli et al pulsed DCs with LY6E peptide (a protein related to MHC class I/II) and then cocultured DCs with mouse splenocytes to assess the ability of DCs to activate T cells. The results suggested that DCs pulsed with LY6E peptide antigen strongly matured and activated T cells . Tumor lysate and tumor-derived exosomes are also used to activate DCs, and the results show that they can induce T cell activation and proliferation. , Moreover, it avoids the limitation of antigen selection and is accepted widely by patients. , All of these approaches have been successful and are simple and cheap.…”

Dendritic Cell-Based Immunotherapies and their Potential use in Colorectal Cancer Immunotherapy

“…In addition, DCs are enhancers of the immune response and capable of T-cell activation. [ 7 8 10 11 12 14 15 16 17 18 19 20 21 22 23 24 ] In this review, the mechanism and efficiency of the human conventional type-1 DCs (cDC-1), OX40 + plasmacytoid DCs (pDCs), and DCs-derived exosomes were discussed. In addition, different combinations with DCs therapy such as combination with the monoclonal antibody (mAb), cytokine-induced killer (CIK) cells, adjuvants, chemotherapy (DC-based chemoimmunotherapy), and nanoparticles (NPs) were listed and explored for their effectiveness against cancer, especially against CRC.…”