Data from Downregulation of MHC-I Expression Is Prevalent but Reversible in Merkel Cell Carcinoma

作者：Kelly G. Paulson, Andrew Tegeder, Christoph Willmes, Jayasri G. Iyer, Olga K. Afanasiev, David Schrama, S Koba, Renee Thibodeau, Kotaro Nagase, William Simonson, Aaron Seo, David M. Koelle, Margaret M. Madeleine, Shailender Bhatia, Hideki Nakajima, Shigetoshi Sano, James S. Hardwick, Mary L. Disis, Michele A. Cleary, Jürgen C. Becker, Paul Nghiem · 年份：2023 · DOI：10.1158/2326-6066.c.6548198 · 研究领域：Polyomavirus and related diseases、Plant Virus Research Studies、Bacteriophages and microbial interactions

<div>AbstractMerkel cell carcinoma (MCC) is an aggressive, polyomavirus-associated skin cancer. Robust cellular immune responses are associated with excellent outcomes in patients with MCC, but these responses are typically absent. We determined the prevalence and reversibility of major histocompatibility complex class I (MHC-I) downregulation in MCC, a potentially reversible immune-evasion mechanism. Cell-surface MHC-I expression was assessed on five MCC cell lines using flow cytometry as well as immunohistochemistry on tissue microarrays representing 114 patients. Three additional patients were included who had received intralesional IFN treatment and had evaluable specimens before and after treatment. mRNA expression analysis of antigen presentation pathway genes from 35 MCC tumors was used to examine the mechanisms of downregulation. Of note, 84% of MCCs (total n = 114) showed reduced MHC-I expression as compared with surrounding tissues, and 51% had poor or undetectable MHC-I expression. Expression of MHC-I was lower in polyomavirus-positive MCCs than in polyomavirus-negative MCCs (P < 0.01). The MHC-I downregulation mechanism was multifactorial and did not depend solely on HLA gene expression. Treatment of MCC cell lines with ionizing radiation, etoposide, or IFN resulted in MHC-I upregulation, with IFNs strongly upregulating MHC-I expression in vitro, and in 3 of 3 patients treated with intrales...