Characterization of immune evasion in Merkel cell carcinoma

Merkel cell carcinoma (MCC) is a rare, neuroendocrine skin carcinoma that is caused by the Merkel cell polyomavirus (MCPyV) in 80% of cases and by ultraviolet (UV) damage in 20% of cases. MCC should theoretically elicit a strong cytotoxic T cell response due to the high neoantigen and viral antigen burden in MCPyV- and MCPyV+ MCC, respectively. However, MCC often escapes immune recognition and is associated with very poor prognosis at advanced stages. To systemically identify mechanisms of immune evasion in MCC, we established 11 robust MCC lines from either primary tumors or patient-derived xenografts (7 MCPyV+ and 4 MCPyV-). We then characterized these tumors and cell lines by whole exome sequencing (WES), RNA-sequencing, scRNA-sequencing, ATAC-seq, and whole genome bisulfite... (for more see dbGaP study page.)

默克尔细胞癌（Merkel cell carcinoma, MCC）是一种罕见的神经内分泌皮肤癌，80%的病例由默克尔细胞多瘤病毒（Merkel cell polyomavirus, MCPyV）引发，剩余20%由紫外线（ultraviolet, UV）损伤导致。从理论层面而言，由于MCPyV阳性（MCPyV+）与MCPyV阴性（MCPyV-）的MCC分别承载大量新抗原与病毒抗原负荷，MCC理应触发强烈的细胞毒性T细胞应答。然而，MCC常常能够逃避免疫识别，且在进展期预后极差。为系统性鉴定MCC的免疫逃逸机制，我们分别从原发肿瘤或患者来源异种移植瘤（patient-derived xenografts）中建立了11株性状稳定的MCC细胞系，其中7株为MCPyV阳性，4株为MCPyV阴性。随后我们通过全外显子组测序（whole exome sequencing, WES）、RNA测序、单细胞RNA测序（single-cell RNA sequencing, scRNA-seq）、转座酶可及性染色质测序（assay for transposase-accessible chromatin sequencing, ATAC-seq）以及全基因组亚硫酸氢盐测序等手段对上述肿瘤及细胞系进行了表征，更多详情请参见dbGaP研究页面。