NY-ESO-1 cancer testis antigen demonstrates high immunogenicity in triple negative breast cancer

PLoS One. 2012;7(6):e38783. doi: 10.1371/journal.pone.0038783. Epub 2012 Jun 28.

Abstract

Purpose: NY-ESO-1 cancer testis (CT) antigen is an attractive candidate for immunotherapy as a result of its high immunogenicity. The aim of this study was to explore the potential for NY-ESO-1 antigen directed immunotherapy in triple negative breast cancer (TNBC) by determining the frequency of expression by immunohistochemistry (IHC) and the degree of inherent immunogenicity to NY-ESO-1.

Experimental design: 168 TNBC and 47 ER+/HER2- primary breast cancer specimens were used to determine NY-ESO-1 frequency by IHC. As previous studies have shown that patients with a robust innate humoral immune response to CT antigens are more likely to develop CD8 T-cell responses to NY-ESO-1 peptides, we evaluated the degree to which patients with NY-ESO-1 expression had inherent immunogenicity by measuring antibodies. The relationship between NY-ESO-1 expression and CD8+ T lymphocytes was also examined.

Results: The frequency of NY-ESO-1 expression in the TNBC cohort was 16% versus 2% in ER+/HER2- patients. A higher NY-ESO-1 score was associated with a younger age at diagnosis in the TNBC patients with NY-ESO-1 expression (p = 0.026). No differences in OS (p = 0.278) or PFS (p = 0.238) by NY-ESO-1 expression status were detected. Antibody responses to NY-ESO-1 were found in 73% of TNBC patients whose tumors were NY-ESO-1 positive. NY-ESO-1 positive patients had higher CD8 counts than negative patients (p = 0.018).

Conclusion: NY-ESO-1 is expressed in a substantial subset of TNBC patients and leads to a high humoral immune response in a large proportion of these individuals. Given these observations, patients with TNBC may benefit from targeted therapies directed against NY-ESO-1.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Neoplasm / blood*
  • Antigens, Neoplasm / immunology*
  • Antigens, Neoplasm / metabolism
  • Breast Neoplasms / immunology*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / mortality
  • CD8-Positive T-Lymphocytes
  • Carcinoma, Ductal, Breast / immunology*
  • Carcinoma, Ductal, Breast / metabolism
  • Carcinoma, Ductal, Breast / mortality
  • Carcinoma, Lobular / immunology*
  • Carcinoma, Lobular / metabolism
  • Carcinoma, Lobular / mortality
  • DNA Methylation
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Immunoenzyme Techniques
  • Membrane Proteins / immunology
  • Membrane Proteins / metabolism*
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Recurrence, Local / immunology*
  • Neoplasm Recurrence, Local / metabolism
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Staging
  • Prognosis
  • Receptor, ErbB-2 / metabolism
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism
  • Survival Rate

Substances

  • Antibodies, Neoplasm
  • Antigens, Neoplasm
  • CTAG1B protein, human
  • Membrane Proteins
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Receptor, ErbB-2