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PLoS One ; 7(6): e38783, 2012.
Article in English | MEDLINE | ID: mdl-22761704

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.


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