NCOR2 represses MHC class I molecule expression to drive metastatic progression of breast cancer.
basic_science · Level V
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- Record sourced from PubMed, PMID 42086546.
- Also identified by DOI 10.1038/s41467-026-72168-3.
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Abstract
Metastatic progression depends upon the ability of disseminated tumor cells to evade immune surveillance. Major Histocompatibility Complex (MHC)-mediated antigen presentation facilitates T cell-dependent eradication of metastatic tumor cells. Here, we show that nuclear corepressor 2 (NCOR2) is an epigenetic regulator of MHC class I molecule presentation on breast tumor cells. Patients with triple negative breast cancer (TNBC) that express high levels of NCOR2 also exhibit reduced metastasis-free survival and decreased MHC class I expression, and the metastatic lesions in patients with TNBC have high nuclear NCOR2 and reduced Cluster of Differentiation (CD)8<sup>+</sup> T cells. Reducing NCOR2 expression or preventing its interaction with Histone Deacetylase, HDAC3, enhances innate immune cell recruitment and activity, and elevates MHC class I levels on disseminated cancer cells to potentiate CD8<sup>+</sup> T cell activity and apoptosis induction that prevents metastatic progression. The studies provide evidence to support NCOR2 as a targetable epigenetic regulator of metastasis towards which therapies could be developed to reduce patient mortality.