Details

Autor(en) / Beteiligte

• Lee, Patrick C
• Klaeger, Susan
• Le, Phuong M
• Korthauer, Keegan
• Cheng, Jingwei
• Ananthapadmanabhan, Varsah
• Frost, Thomas C
• Stevens, Jonathan D
• Wong, Alan Y.L
• Iorgulescu, Bryan

Titel

Reversal of viral and epigenetic HLA class I repression in Merkel cell carcinoma

Ist Teil von

• The Journal of clinical investigation, 2022-07, Vol.132 (13), p.1-16

Ort / Verlag

Ann Arbor: American Society for Clinical Investigation

Erscheinungsjahr

2022

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Cancers avoid immune surveillance through an array of mechanisms, including perturbation of HLA class I antigen presentation. Merkel cell carcinoma (MCC) is an aggressive, HLA-I-low, neuroendocrine carcinoma of the skin often caused by the Merkel cell polyomavirus (MCPyV). Through the characterization of 11 newly generated MCC patient-derived cell lines, we identified transcriptional suppression of several class I antigen presentation genes. To systematically identify regulators of HLA-I loss in MCC, we performed parallel, genome-scale, gain- and loss-of-function screens in a patient-derived MCPyV-positive cell line and identified MYCL and the non-canonical Polycomb repressive complex 1.1 (PRC1.1) as HLA-I repressors. We observed physical interaction of MYCL with the MCPyV small T viral antigen, supporting a mechanism of virally mediated HLA-I suppression. We further identify the PRC1.1 component USP7 as a pharmacologic target to restore HLA-I expression in MCC.