Detection of autoantibodies against cancer-testis antigens in non-small cell lung cancer

Lung Cancer. 2018 Nov:125:157-163. doi: 10.1016/j.lungcan.2018.09.012. Epub 2018 Sep 17.

Abstract

Objectives: Cancer-testis antigens (CTAs) are defined as proteins that are specifically expressed in testis or placenta and their expression is frequently activated in cancer. Due to their ability to induce an immune response, CTAs may serve as suitable targets for immunotherapy. The aim of this study was to evaluate if there is reactivity against CTAs in the plasma of non-small cell lung cancer (NSCLC) patients through the detection of circulating antibodies.

Materials and methods: To comprehensively analyze autoantibodies against CTAs the multiplexing capacities of suspension bead array technology was used. Bead arrays were created with 120 protein fragments, representing 112 CTAs. Reactivity profiles were measured in plasma samples from 133 NSCLC patients and 57 cases with benign lung diseases.

Results: Altogether reactivity against 69 antigens, representing 81 CTAs, was demonstrated in at least one of the analyzed samples. Twenty-nine of the antigens (45 CTAs) demonstrated exclusive reactivity in NSCLC samples. Reactivity against cancer-testis antigen family 47; member A (CT47A) genes, P antigen family member 3 (PAGE3), variable charge X-linked (VCX), melanoma antigen family B1 (MAGEB1), lin-28 homolog B (LIN28B) and chromosome 12 open reading frame 54 (C12orf54) were only found in NSCLC patients at a frequency of 1%-4%. The presence of autoantibodies towards these six antigens was confirmed in an independent group of 34 NSCLC patients.

Conclusion: We identified autoantibodies against CTAs in the plasma of lung cancer patients. The reactivity pattern of autoantibodies was higher in cancer patients compared to the benign group, stable over time, but low in frequency of occurrence. The findings suggest that some CTAs are immunogenic and that these properties can be utilized as immune targets.

Keywords: Adenocarcinoma; Cancer immunity; Lung cancer; MAGE; Squamous cell cancer; Tumor markers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm / immunology
  • Autoantibodies / immunology*
  • Biomarkers, Tumor / immunology
  • Carcinoma, Non-Small-Cell Lung / immunology*
  • Carcinoma, Non-Small-Cell Lung / therapy*
  • Female
  • Humans
  • Immunotherapy / methods
  • Lung Neoplasms / immunology*
  • Lung Neoplasms / therapy*
  • Male
  • Membrane Proteins / immunology
  • Neoplasm Proteins / immunology
  • Testis / immunology*

Substances

  • Antigens, Neoplasm
  • Autoantibodies
  • Biomarkers, Tumor
  • Membrane Proteins
  • Neoplasm Proteins