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<p>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,&#xa0;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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月5日

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  • Pavla Ticha,
  • Jason J. Northey,
  • Radhika Narain,
  • Shivang Sharma,
  • Johnathon N. Lakins,
  • Hugo Gonzalez,
  • Kelly Kersten,
  • Alastair J. Ironside,
  • Allison P. Drain,
  • Martin Zidek,
  • Kelvin K. Tsai,
  • Yunn-Yi Chen,
  • Eugene Shenderov,
  • Valerie M. Weaver

摘要

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+ 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+ 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.