NCOR2 represses MHC class I molecule expression to drive metastatic progression of breast cancer

MHC-mediated antigen presentation facilitates T cell-dependent eradication of metastatic tumor cells. We identified nuclear corepressor 2 (NCOR2) as an epigenetic regulator of MHC class I molecule presentation on breast tumor cells.

Patients with triple negative breast cancers (TNBC) that expressed high levels of NCOR2 also exhibited reduced metastasis-free survival and decreased MHC class I expression, and metastatic lesions in patients with TNBC had high nuclear NCOR2 and reduced CD8+ T cells. Reducing NCOR2 expression or preventing its interaction with HDAC3 enhanced innate immune cell recruitment and activity, and elevated MHC class I levels on disseminated cancer cells to potentiate CD8+ T cell activity and apoptosis induction that prevented metastatic progression.