Selenocompounds mediated upregulation of HLA class I expression enhanced mammaglobin-A peptide-specific cytotoxic T lymphocyte responses against breast cancer cells

Abstract

Abstract Recent phase I DNA vaccine clinical trials with Mammaglobin-A (Mam-A), a human breast tumor-associated antigen (TAA), have shown to be safe and efficient. However, the success of cancer vaccines is limited by the diminished expression of HLA class I molecules on cancer cells. In our current communication, we studied the impact of various selenocompounds towards the expression of HLA class I molecules on breast cancer cells and their impact on the cytotoxicity of MamA2.1 (HLA-A2 immunodominant epitope of Mam-A) activated human CD8+T lymphocytes (hCTLs). We noted an enhanced HLA-A2 expression along with upregulation of components involved in antigen presentation machinery in all four breast cancer cell lines, namely AU565, UACC-812, MCF-7, and MDA-MB-231, following treatment with methyselenol producing methylseninic acid (MSA) and dimethylselenide (DMDSe). Furthermore, we have demonstrated enhanced cytotoxicity of MamA2.1 activated CTLs on HLA-A2+/Mam-A+ AU565 and UACC-812 cell lines following pre-treatment with MSA and DMDSe, while no significant toxicity was noted under similar conditions on HLA-A2+/Mam-A− MCF-7 and MDA-MB-231 breast cancer cell lines. Taken together, our data demonstrated that MSA and DMDSe potentiate effector cytotoxic responses following TAA vaccine specific activation of CD8+T lymphocytes, and thus suggesting their futuristic role as vaccine adjuvants in cancer immunotherapy.