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Optimization of a Multiplex RNA-based Expression Assay Using Breast Cancer Archival Material
Published on: August 1, 2018
NY-ESO-1 cancer testis antigen demonstrates high immunogenicity in triple negative breast cancer
Foluso O Ademuyiwa1, Wiam Bshara, Kristopher Attwood
1Department of Medicine, Roswell Park Cancer Institute, Buffalo, New York, United States of America. foluso.ademuyiwa@roswellpark.org
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.
Insights
NY-ESO-1 is expressed in 16% of triple-negative breast cancer (TNBC) tumors, eliciting a strong immune response. This suggests TNBC patients may benefit from NY-ESO-1 targeted immunotherapies.
Area of Science:
- Oncology
- Immunology
- Cancer Research
Background:
- NY-ESO-1 is a cancer-testis antigen with high immunogenicity, making it a promising target for cancer immunotherapy.
- Triple-negative breast cancer (TNBC) is an aggressive subtype with limited targeted therapy options.
Purpose of the Study:
- To investigate the expression frequency of NY-ESO-1 in TNBC and its association with immunogenicity.
- To explore the potential of NY-ESO-1 directed immunotherapy in TNBC.
Main Methods:
- Immunohistochemistry (IHC) was used to assess NY-ESO-1 expression in 168 TNBC and 47 ER+/HER2- breast cancer specimens.
- Antibody responses to NY-ESO-1 were measured to evaluate inherent immunogenicity.
- CD8+ T lymphocyte counts were examined in relation to NY-ESO-1 expression.
Main Results:
- NY-ESO-1 was expressed in 16% of TNBC cases, compared to 2% in ER+/HER2- cases.
- 73% of NY-ESO-1 positive TNBC patients showed antibody responses.
- NY-ESO-1 positive patients had significantly higher CD8+ T lymphocyte counts.
Conclusions:
- NY-ESO-1 expression is prevalent in a significant subset of TNBC.
- NY-ESO-1 expression correlates with a robust humoral immune response and increased CD8+ T cells in TNBC.
- These findings support the potential benefit of NY-ESO-1 targeted therapies for TNBC patients.
