Epigenetic Regulation of the Melanoma Microenvironment
Abstract
Deregulation of epigenetic states promotes melanoma progression. MacroH2A, a histone variant associated with transcriptional repression, is downregulated in melanoma vs. benign nevi, where it suppresses proliferation and metastatic potential. However, its role as a barrier to tumorigenesis has not been investigated in vivo. We found that mice constitutively lacking macroH2A variants exhibit accelerated melanoma growth compared to their wild-type counterparts. MacroH2A-deficient tumors display impaired cytotoxic T cell function and increased monocyte infiltration, consistent with a compromised anti-tumor immune response, as well as upregulation of Ccl2, Cxcl1 and Il6, which are myeloid chemo-attractants. Through single-cell transcriptomic profiling of the entire melanoma microenvironment, we identified alterations in the immune cell compartment in macroH2A-deficient tumors. Altogether, our data supports a novel tumor suppressor role for macroH2A through repression of pro-inflammatory signaling within the melanoma microenvironment.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2023
- Accession Number
- AD1223162
Entities
People
- Emily Bernstein
Organizations
- Icahn School of Medicine at Mount Sinai