Expression of four cancer-testis antigens in TNBC indicating potential universal immunotherapeutic targets

J Cancer Res Clin Oncol. 2023 Nov;149(16):15003-15011. doi: 10.1007/s00432-023-05274-0. Epub 2023 Aug 23.

Abstract

Objective: Immunotherapy is an attractive treatment for breast cancer. Cancer-testis antigens (CTAs) are potential targets for immunotherapy for their restricted expression. Here, we investigate the expression of CTAs in breast cancer and their value for prognosis. So as to hunt for a potential panel of CTAs for universal immunotherapeutic targets.

Material and methods: A total of 137 breast cancer tissue specimens including 51 triple-negative breast cancer (TNBC) were assessed for MAGE-A4, MAGEA1, NY-ESO-1, KK-LC-1 and PRAME expression by immunohistochemistry. The expression of PD-L1 and TILs was also calculated and correlated with the five CTAs. Clinical data were collected to evaluate the CTA's value for prognosis. Data from the K-M plotter were used as a validation cohort.

Results: The expression of MAGE-A4, NY-ESO-1 and KK-LC-1 in TNBC was significantly higher than in non-TNBC (P = 0.012, P = 0.005, P < 0.001 respectively). 76.47% of TNBC expressed at least one of the five CTAs. Patients with positive expression of either MAGE-A4 or PRAME had a significantly extended disease-free survival (DFS). Data from the Kaplan-Meier plotter confirm our findings.

Conclusions: MAGE-A4, NY-ESO-1, PRAME and KK-LC-1 are overexpressed in breast cancer, especially in TNBC. Positive expression of MAGE-A4 or PARME may be associated with prolonged DFS. A panel of CTAs is attractive universal targets for immunotherapy.

Keywords: Cancer-testis antigens; Immunohistochemistry; Target; Triple-negative breast cancer.

MeSH terms

  • Antigens, Neoplasm / metabolism
  • Biomarkers, Tumor / metabolism
  • Humans
  • Immunotherapy
  • Male
  • Membrane Proteins / metabolism
  • Testis
  • Triple Negative Breast Neoplasms* / metabolism
  • Triple Negative Breast Neoplasms* / therapy

Substances

  • Biomarkers, Tumor
  • Membrane Proteins
  • Antigens, Neoplasm
  • PRAME protein, human