CTLA‑4 blockade combined with 5‑aza‑2'‑deoxycytidine enhances the killing effect of MAGE‑A family common antigen peptide‑specific cytotoxic T cells on breast cancer.

Abstract

Breast cancer is the leading cause of cancer‑-associated deaths in women. Combination immunotherapy attracts great interest as a treatment for breast cancer. However, there are no studies on the use of cytotoxic T‑lymphocyte antigen 4 (CTLA‑4) monoclonal antibody in combination with the melanoma‑associated antigen A family (MAGE‑As) co‑antigen peptide (p248V9) for treating breast cancer, which should be explored. To this aim, in the present study, the samples of 115patients with breast cancer were collected, and MAGE‑As and CTLA‑4 levels in breast cancer and adjacent normal tissues were assessed by immunohistochemical staining. The effect of 5‑aza‑2'‑deoxycytidine (5DC) on the expression of MAGE‑As in breast cancer cell lines was assessed by reverse transcription‑quantitative PCR and western blot assay. Cytotoxic T cells (CTLs) were induced by MAGE‑As co‑antigen peptide. The specific lytic rate and IFN‑γ level were examined by CCK‑8 assay and ELISA, respectively. It was found that MAGE‑As were highly expressed in breast cancer tissues. 5DC treatment promoted the expression of MAGE‑As in breast cancer cells. The upregulation of the expression of MAGE‑As specifically enhanced the ability of CTLs to kill breast cancer cells. CTLA‑4 was highly expressed in breast cancer tissues and cells, and patients with breast cancer exhibiting high expression of CTLA‑4 had low overall survival. CTLA‑4 promoted the lytic efficiency of CTLs in breast cancer cells, and the combination of an anti‑CTLA‑4 antibody and 10µM 5DC exhibited the highest cell lysis ability of CTLs. The present study demonstrated that MAGE‑As co‑antigen peptide‑specific CTLs in combination with an anti‑CTLA‑4 monoclonal antibody and 5DC, have potent tumor cell‑killing effects. It provides a novel theory for the development of breast cancer therapies.