MAGEA10 gene expression in non-small cell lung cancer and A549 cells, and the affinity of epitopes with the complex of HLA-A(∗)0201 alleles

Cell Immunol. 2015 Sep;297(1):10-8. doi: 10.1016/j.cellimm.2015.05.004. Epub 2015 Jun 6.

Abstract

MAGEA10, a cancer/testis antigens expressed in tumors but not in normal tissues with the exception of testis and placenta, represents an attractive target for cancer immunotherapy. However, suppressive cytoenvironment and requirement of specific HLA-alleles presentation frequently led to immunotherapy failure. In this study MAGEA10 was scarcely expressed in cancer patients, but enhanced by viili polysaccharides, which indicates a possibility of increasing epitopes presentation. Furthermore the correlation of gene expression with methylation, indicated by R(2) value for MAGEA10 that was 3 times higher than the value for other MAGE genes tested, provides an explanation of why MAGEA10 was highly inhibited, this is also seen by Kaplan-Meier analysis because MAGEA10 did not change the patients' lifespan. By using Molecular-Docking method, 3 MAGEA10 peptides were found binding to the groove position of HLA-A(∗)0210 as same as MAGEA4 peptide co-crystallized with HLA-A(∗)0210, which indicates that they could be promising for HLA-A(∗)0201 presentation in immunotherapy.

Keywords: Cancer/tissue antigen (CTA); Epitopes; Gene expression/methylation; HLA-A(∗)0201; MAGEA10.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Antigens, Neoplasm / biosynthesis
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / metabolism*
  • Binding Sites
  • Carcinoma, Non-Small-Cell Lung / immunology
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Cell Line, Tumor
  • DNA Methylation / genetics
  • Epitopes, T-Lymphocyte / biosynthesis
  • Epitopes, T-Lymphocyte / immunology*
  • Gene Expression
  • Gene Expression Regulation, Neoplastic
  • HLA-A2 Antigen / genetics
  • HLA-A2 Antigen / immunology*
  • Humans
  • Immunotherapy / methods
  • Lung Neoplasms / immunology
  • Lung Neoplasms / metabolism*
  • Molecular Docking Simulation
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Protein Binding
  • T-Lymphocytes, Cytotoxic / immunology

Substances

  • Antigens, Neoplasm
  • Epitopes, T-Lymphocyte
  • HLA-A*02:01 antigen
  • HLA-A2 Antigen
  • MAGEA10 protein, human
  • MAGEA4 protein, human
  • Neoplasm Proteins