{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T02:05:58Z","timestamp":1784167558786,"version":"3.55.0"},"posted":{"date-parts":[[2026,7,13]]},"group-title":"Cancer Biology","reference-count":46,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T00:00:00Z","timestamp":1783900800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01CA284690"],"award-info":[{"award-number":["R01CA284690"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01CA187718"],"award-info":[{"award-number":["R01CA187718"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Cancer Institute","award":["P01CA281867"],"award-info":[{"award-number":["P01CA281867"]}]},{"name":"National Cancer Institute","award":["T32CA288356"],"award-info":[{"award-number":["T32CA288356"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Merkel cell carcinoma (MCC) is a neuroendocrine skin tumor that is frequently driven by integration of Merkel cell polyomavirus (MCPyV). In MCC, the MCPyV genome is truncated, but expression of the viral tumor antigens, truncated large tumor antigen (LTT) and small tumor antigen (sT), is maintained and drives uncontrolled proliferation. We introduced constitutive expression of the MCPyV T antigens (TAs) into primary mouse dermal fibroblasts (MDFs) to determine whether these cells are susceptible to MCPyV-driven transformation. TA expression alone in MDFs induced key MCC markers, cytokeratin-20 (CK20) and Sry-box transcription factor 2 (SOX2), and promoted anchorage-independent growth indicative of cellular transformation. Subcutaneous implantation of TA-transformed fibroblasts produced high-grade MCC-like tumors that grew persistently in immunodeficient NSG mice but not in immunocompetent C57BL\/6 mice. Serial\n                  <jats:italic>in vivo<\/jats:italic>\n                  passaging of the tumor cell line enhanced tumor growth, reduced expression of p53-target genes and MHC-1, and was accompanied by a shift in T antigen isoform expression, with decreased LTT and increased sT expression. Our data demonstrate that MCPyV-driven tumors acquire immune-evasive adaptions during tumor progression\n                  <jats:italic>in vivo<\/jats:italic>\n                  and suggest that the anti-tumor immune response exerts selective pressure in MCC that favors expression of sT rather than LTT. The model established in this study provides a unique platform for studying evolution of MCPyV-driven tumors under immune pressure and identifying mechanisms of immune evasion in MCC that could be used to develop new therapeutic strategies.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Significance Statement<\/jats:title>\n                  <jats:p>\n                    MCPyV tumor antigen expression transforms mouse dermal fibroblasts to generate MCC-like tumors. Serial\n                    <jats:italic>in vivo<\/jats:italic>\n                    passaging reveals tumor evolution under immune pressure, providing a model to study immune evasion mechanisms in MCC.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.07.10.737822","type":"posted-content","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T16:00:49Z","timestamp":1783958449000},"source":"Crossref","is-referenced-by-count":0,"title":["An immunocompetent model of MCPyV-driven Merkel cell carcinoma reveals tumor evolution under immune selection"],"prefix":"10.64898","author":[{"given":"James M","family":"Regan","sequence":"first","affiliation":[{"name":"Department of Microbiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Microbiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mykaela","family":"Salvacion","sequence":"additional","affiliation":[{"name":"Department of Microbiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiana","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Microbiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Microbiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace","family":"Ho","sequence":"additional","affiliation":[{"name":"Department of Microbiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan R","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Perelman School of Medicine University of Pennsylvania, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shujing","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Perelman School of Medicine University of Pennsylvania, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Perelman School of Medicine University of Pennsylvania, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowei","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Perelman School of Medicine University of Pennsylvania, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianxin","family":"You","sequence":"additional","affiliation":[{"name":"Department of Microbiology"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026071518550851000_2026.07.10.737822v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cll.2017.05.004"},{"key":"2026071518550851000_2026.07.10.737822v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2017.10.028"},{"key":"2026071518550851000_2026.07.10.737822v1.3","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-018-0103-2"},{"key":"2026071518550851000_2026.07.10.737822v1.4","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.ejca.2022.03.043","article-title":"Diagnosis and treatment of Merkel cell carcinoma: European consensus-based interdisciplinary guideline - Update 2022","volume":"171","year":"2022","journal-title":"Eur J Cancer"},{"key":"2026071518550851000_2026.07.10.737822v1.5","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1603702"},{"key":"2026071518550851000_2026.07.10.737822v1.6","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-13-0034"},{"key":"2026071518550851000_2026.07.10.737822v1.7","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.jaad.2021.04.024","article-title":"Clinical impact of immunotherapy in Merkel cell carcinoma patients: A systematic review and meta-analysis","volume":"87","year":"2022","journal-title":"J Am Acad Dermatol"},{"key":"2026071518550851000_2026.07.10.737822v1.8","doi-asserted-by":"publisher","DOI":"10.1126\/science.1152586"},{"key":"2026071518550851000_2026.07.10.737822v1.9","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-15-0702"},{"key":"2026071518550851000_2026.07.10.737822v1.10","doi-asserted-by":"crossref","unstructured":"K. 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