| First Author | Burr ML | Year | 2019 |
| Journal | Cancer Cell | Volume | 36 |
| Issue | 4 | Pages | 385-401.e8 |
| PubMed ID | 31564637 | Mgi Jnum | J:279996 |
| Mgi Id | MGI:6363904 | Doi | 10.1016/j.ccell.2019.08.008 |
| Citation | Burr ML, et al. (2019) An Evolutionarily Conserved Function of Polycomb Silences the MHC Class I Antigen Presentation Pathway and Enables Immune Evasion in Cancer. Cancer Cell 36(4):385-401.e8 |
| abstractText | Loss of MHC class I (MHC-I) antigen presentation in cancer cells can elicit immunotherapy resistance. A genome-wide CRISPR/Cas9 screen identified an evolutionarily conserved function of polycomb repressive complex 2 (PRC2) that mediates coordinated transcriptional silencing of the MHC-I antigen processing pathway (MHC-I APP), promoting evasion of T cell-mediated immunity. MHC-I APP gene promoters in MHC-I low cancers harbor bivalent activating H3K4me3 and repressive H3K27me3 histone modifications, silencing basal MHC-I expression and restricting cytokine-induced upregulation. Bivalent chromatin at MHC-I APP genes is a normal developmental process active in embryonic stem cells and maintained during neural progenitor differentiation. This physiological MHC-I silencing highlights a conserved mechanism by which cancers arising from these primitive tissues exploit PRC2 activity to enable immune evasion. |
