The Role of the Cancer Testis Antigen PRAME in Cancer Hallmark Acquisition of Triple Negative Breast Cancer

PReferentially expressed Antigen in Melanoma (PRAME) have been the focus of many clinical immunotherapy trials due to its restricted expression in normal cells, re-expression in tumor cells and immunogenicity. However, the biological function of PRAME and the interplay of PRAME expression with the tumor immune microenvironment remains unexplored. In this study, we investigated if PRAME overexpression in MDA-MB-468 triple negative breast cancer (TNBC) cells is involved in the acquisition of hallmarks of cancer. Further, we explored whether PRAME expression is involved in the modulation of the anti-tumor immune response and the regulation of miRNA-mRNA networks. Further, we investigated the possible epigenetic mechanisms involved in regulating PRAME re-expression in cancer. The role of PRAME in the acquisition of different hallmarks of cancer was investigated using gain‑ and loss‑of‑function TNBC cell line models. We demonstrated that PRAME facilitates the transition to a mesenchymal phenotype through reprogramming of several EMT-genes, resulting in enhanced migration and invasion of triple negative breast cancer cells. Moreover, PRAME re-expression in triple negative breast tumors dysregulates several miRNA-mRNA regulatory networks that can modulate tumor cell survival and the anti-tumor immune response. Further, PRAME expression mediate immunosuppression through different mechanisms involving deregulation of several genes involved in anti-inflammatory and antitumor immune responses resulting in an immunosuppressive tumor microenvironment (TME).To conclude, our findings support the potential role of PRAME as novel prognostic and immunotherapeutic target in PRAME positive tumors.