Immune Responses to the Cancer Testis Antigen XAGE-1b in Non Small Cell Lung Cancer Caucasian Patients

PLoS One. 2016 Mar 3;11(3):e0150623. doi: 10.1371/journal.pone.0150623. eCollection 2016.

Abstract

Immunotherapy approaches using checkpoint blockade, alone, or in combination with tumor antigen vaccination, or adoptive cell transfer, are emerging as promising approaches for the treatment of non-small cell lung cancer (NSCLC). In preparation for upcoming combined immunotherapy approaches in NSCLC, here, we have assessed spontaneous immune responses to XAGE-1b, a tumor specific antigen of the Cancer Testis Antigen group that has been previously reported to be spontaneously immunogenic in the Japanese population, in a cohort of Caucasian patients with NSCLC. We found spontaneous serological responses to XAGE-1b in 9% of the patients. Importantly, these responses were limited to, and represented 13% of, patients with adenocarcinoma tumors, the most frequent histological subtype, for which immunotherapy approaches are under development. Using a set of overlapping peptides spanning the entire XAGE-1b protein, and in support of the serological data, we detected significant XAGE-1b specific CD4+ T cell responses in all XAGE-1b seropositive patients and identified several CD4+ T cell epitopes. Altogether, our results support the relevance of the XAGE-1b antigen in Caucasians NSCLC patients with adenocarcinoma, and the implementation of future immunotherapies exploiting the high immunogenicity of the antigen in this patient population.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / immunology
  • Adenocarcinoma / pathology
  • Adenocarcinoma / therapy*
  • Amino Acid Sequence
  • Antigens, Neoplasm / administration & dosage
  • Antigens, Neoplasm / chemistry
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / immunology*
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / pathology
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / pathology
  • Cancer Vaccines / administration & dosage
  • Cancer Vaccines / biosynthesis
  • Cancer Vaccines / immunology
  • Carcinoma, Non-Small-Cell Lung / immunology
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / therapy*
  • Case-Control Studies
  • Epitopes / chemistry
  • Epitopes / immunology
  • Gene Expression
  • Humans
  • Immunotherapy, Active / methods
  • Interferon-gamma / agonists
  • Interferon-gamma / biosynthesis
  • Lung Neoplasms / immunology
  • Lung Neoplasms / pathology
  • Lung Neoplasms / therapy*
  • Molecular Sequence Data
  • Peptides / administration & dosage
  • Peptides / chemistry
  • Peptides / immunology
  • Primary Cell Culture

Substances

  • Antigens, Neoplasm
  • Cancer Vaccines
  • Epitopes
  • Peptides
  • XAGE1A protein, human
  • Interferon-gamma

Grants and funding

This study was supported by the Ludwig Institute for Cancer Research (USA), the Cancer Research Institute (USA), Ligue contre le Cancer (France) and LabeX IGO (France). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.