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Antibody responses to NY-ESO-1 in primary breast cancer identify a subtype target for immunotherapy
Ahmed Hamaï1, Karine Duperrier-Amouriaux, Pascale Pignon
1Institut National de la Santé et de la Recherche Médicale, Unité 892, CLCC René Gauducheau, Saint Herblain, France.
Abstract:
The highly immunogenic human tumor antigen NY-ESO-1 (ESO) is a target of choice for anti-cancer immune therapy. In this study, we assessed spontaneous antibody (Ab) responses to ESO in a large cohort of patients with primary breast cancer (BC) and addressed the correlation between the presence of anti-ESO Ab, the expression of ESO in the tumors and their characteristics. We found detectable Ab responses to ESO in 1% of the patients. Tumors from patients with circulating Ab to ESO exhibited common characteristics, being mainly hormone receptor (HR)⁻ invasive ductal carcinomas of high grade, including both HER2⁻ and HER2⁺ tumors. In line with these results, we detected ESO expression in 20% of primary HR⁻ BC, including both ESO Ab⁺ and Ab⁻ patients, but not in HR⁺ BC. Interestingly, whereas expression levels in ESO⁺ BC were not significantly different between ESO Ab⁺ and Ab⁻ patients, the former had, in average, significantly higher numbers of tumor-infiltrated lymph nodes, indicating that lymph node invasion may be required for the development of spontaneous anti-tumor immune responses. Thus, the presence of ESO Ab identifies a tumor subtype of HR⁻ (HER2⁻ or HER2⁺) primary BC with frequent ESO expression and, together with the assessment of antigen expression in the tumor, may be instrumental for the selection of patients for whom ESO-based immunotherapy may complement standard therapy.
Insights
One percent of breast cancer patients show an antibody response to the NY-ESO-1 (ESO) antigen. This response is linked to specific tumor characteristics, suggesting a potential role for ESO-based immunotherapy.
Area of Science:
- Oncology
- Immunology
- Cancer Research
Background:
- The human tumor antigen NY-ESO-1 (ESO) is highly immunogenic and a promising target for anti-cancer immune therapies.
- Understanding spontaneous immune responses to tumor antigens is crucial for developing effective immunotherapies.
Purpose of the Study:
- To assess spontaneous antibody (Ab) responses to NY-ESO-1 (ESO) in primary breast cancer (BC) patients.
- To correlate anti-ESO Ab presence with ESO expression and tumor characteristics.
- To identify patient subgroups that may benefit from ESO-based immunotherapy.
Main Methods:
- Analysis of a large cohort of primary breast cancer patients.
- Detection of circulating antibodies to ESO.
- Assessment of ESO expression in tumor tissues.
- Correlation analysis of antibody status, antigen expression, and clinicopathological features (hormone receptor status, HER2 status, tumor grade, lymph node invasion).
Main Results:
- Detectable anti-ESO Ab responses were found in 1% of BC patients.
- Tumors from anti-ESO Ab-positive patients were predominantly hormone receptor-negative (HR⁻), high-grade invasive ductal carcinomas (both HER2⁻ and HER2⁺).
- ESO expression was detected in 20% of primary HR⁻ BC, irrespective of antibody status, but not in HR⁺ BC.
- Anti-ESO Ab-positive patients had significantly higher numbers of tumor-infiltrated lymph nodes compared to antibody-negative patients with ESO-expressing tumors.
Conclusions:
- The presence of anti-ESO antibodies identifies a specific subtype of primary HR⁻ breast cancer (HER2⁻ or HER2⁺) with frequent ESO expression.
- Lymph node invasion may be a prerequisite for developing spontaneous anti-tumor immune responses against ESO.
- Assessing both anti-ESO antibodies and tumor antigen expression can aid in selecting patients for ESO-based immunotherapy to complement standard treatments.
