NY-ESO-1 in Triple-Negative Breast Cancer: Systematic Review, Meta-Analysis, and Immunotherapeutic Implications

Clinical Snapshot

Key Findings

• P Value: p<0.0001 for antibody clone comparison, p<0.001 for scoring method comparison

• Effect Size: Pooled prevalence 16.1%

• Primary Outcome: NY-ESO-1 expression prevalence in TNBC

• Nnt Or Sensitivity: Detection sensitivity varies significantly: E978 clone 15.1% vs D8.38 clone 32.6%

• Confidence Interval: 95% CI: 11.4-22.2%

Clinical Application

Limited by lack of standardised detection protocols and high methodological heterogeneity Relevant for Australian oncology practice, though TGA approval status of NY-ESO-1 targeted therapies unclear. May inform PBS considerations for future immunotherapeutic agents TNBC patients being considered for NY-ESO-1 targeted immunotherapy

Abstract

Breast cancer remains one of the most common types of cancer, including the subtype triple-negative breast cancer (TNBC) which is challenging to treat due to its aggressiveness. Cancer-testis antigens (CTAs), especially New York Esophageal Squamous Cell Carcinoma 1 (NY-ESO-1), have become promising immunotherapeutic targets attributable to their restricted expression profile in normal tissues but overexpressed in TNBC, leading to immunogenicity. This review provides comprehensive discussion of NY-ESO-1 including its structural basis of NY-ESO-1 recognition by T cell receptors (TCRs) and antibodies, epigenetic regulation via DNA methylation or histone modifications, and expression patterns or clinical relevance in TNBC. A systematic meta-analysis of 12 studies comprising 1,545 TNBC patients showed a pooled NY-ESO-1 expression prevalence of 16.1% (95% CI: 11.4-22.2%), with heterogeneity (I2=83.7%) attributable to antibody clone used for NY-ESO-1 detection (E978: 15.1% vs. D8.38: 32.6%, p<0.0001) and scoring methods (composite scoring: 15.9% vs. dual scoring: 16.9% vs. H-score: 10.1% vs. simple threshold: 32.6%, p<0.001). Structural analyses reveal NY-ESO-1157-165 recognition by TCRs, antibodies, and engineered binding scaffolds. We examine preclinical and clinical evidence for NY-ESO-1-targeted therapies, including adoptive cell therapy and peptide vaccines, which show manageable safety profiles and induce immunological responses. Epigenetic regulation is a therapeutic avenue, whereby hypomethylating agents and histone deacetylase inhibitors can upregulate NY-ESO-1 expressions that promote tumor immunogenicity. Nonetheless, challenges persist such as NY-ESO-1 expression heterogeneity, lack of TNBC-specific clinical trials, and inadequate immunogenicity. Future research should standardize NY-ESO-1 detection protocols to identify TNBC patients for NY-ESO-1-targeted immunotherapy, prioritize TNBC-specific trials and combinations with epigenetic priming agents.

References

1. 1.Auni, N. A., Asri, N. M., Redzwan, M., Norhanani, H., Faezahtul Arbaeyah, Y., Maya Mazuwin, A. H., Suzina Sheikh, W., & Kah Keng. (2026). NY-ESO-1 in Triple-Negative Breast Cancer: Systematic Review, Meta-Analysis, and Immunotherapeutic Implications. International Immunopharmacology, 116459. https://doi.org/10.1016/j.intimp.2026.116459