The promyelocytic leukemia PML protein is a key immune suppressor in triple-negative breast cancer

Here, we identify the targetable protein PML as a key mediator of immune evasion in TNBC via independent and converging mechanisms. We demonstrate that PML promotes the establishment of an immunosuppressive tumor microenvironment while concurrently impairing antigen presentation by tumor cells.

Mechanistically, we find that PML partakes to the chronic activation of inflammatory and interferon-γ-responsive signaling, leading to constitutive activation of immunosuppressive genes, including PD-L1. Additionally, PML collaborates with DNMT1 to repress HLA gene expression, thus limiting tumor recognition and killing by cytotoxic T cells. Analysis of human TNBC datasets links high PML expression to impaired immune activation and poor responses to chemotherapy.