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

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

Foluso O Ademuyiwa  1 , Wiam Bshara, Kristopher Attwood, Carl Morrison, Stephen B Edge, Adam R Karpf, Smith A James, Christine B Ambrosone, Tracey L O'Connor, Ellis G Levine, Anthony Miliotto, Erika Ritter, Gerd Ritter, Sacha Gnjatic, Kunle Odunsi
Affiliations

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

Foluso O Ademuyiwa et al. PLoS One. 2012.

Erratum in

  • PLoS One.2012;7(8). doi:10.1371/annotation/5cdf6105-2a52-497a-86b3-db8f4a4e439c. Karpf, Adam R [added]; James, Smith A [added]

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.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. NY-ESO-1 expression by IHC compared with a negative IgG control.
Photomicrograph of NY-ESO-1 expression by immunohistochemistry side by side compared with a negative IgG control.
Figure 2
Figure 2. OS by NY-ESO-1 expression in TNBC.
Kaplan-Meier curve showing OS differences in patients with TNBC stratified by NY-ESO-1 expression.
Figure 3
Figure 3. PFS by NY-ESO-1 expression in TNBC.
Kaplan-Meier curve showing PFS differences in patients with TNBC stratified by NY-ESO-1 expression.
Figure 4
Figure 4. Extent of CD8 infiltration in triple negative tumors.
This figure demonstrates the extent of CD8 infiltration in triple negative breast specimens.
Figure 5
Figure 5. The relationship between NY-ESO-1 expression and degree of CD8 tumor infiltrating lymphocytes in TNBC.
This figure shows the relationship between NY-ESO-1 expression and degree of CD8 tumor infiltrating lymphocytes in TNBC.
Figure 6
Figure 6. Induction of NY-ESO-1 by decitabine and 5-azacytidine.
Photomicrograph showing the ability of decitabine and 5-azacytidine to induce of NY-ESO-1 in vitro in MCF-7 cells.
Figure 7
Figure 7. NY-ESO-1 promoter methylation was reduced by both decitabine and 5-azacytidine in MCF-7 cells.
Graph showing that NY-ESO-1 promoter methylation was reduced by both decitabine and 5-azacytidine in MCF-7 cells.
See this image and copyright information in PMC

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