{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T13:23:02Z","timestamp":1791897782431,"version":"4.3.4"},"posted":{"date-parts":[[2025,10,20]]},"group-title":"Cancer Biology","reference-count":38,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T00:00:00Z","timestamp":1760918400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,10,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Despite the advent of immunotherapy, human-papilloma-virus (HPV)-negative head and neck squamous cell carcinoma (HNSCC) carries a high morbidity and mortality rate, thus novel therapies are urgently needed. Suppressor Of Variegation 4-20 Homolog 1 (SUV420H1) is a protein lysine methyltransferase that writes H4K20me3. Approximately 35% of HPV-negative HNSCC tumors carry gains\/amplifications of\n                  <jats:italic>SUV420H1<\/jats:italic>\n                  . Gene Set Enrichment Analysis (GSEA) showed enrichment of proliferation-, epithelial-mesenchymal transition (EMT)- and immune-response pathways in\n                  <jats:italic>SUV420H1<\/jats:italic>\n                  -overexpressing HPV-negative HNSCC tumors. Depletion of SUV420H1 led to decreased proliferation, cell cycling and invasion in human HPV-negative HNSCC cell lines, while enzymatic inhibition decreased the invasive capacity but not the proliferation and cell cycling of HPV-negative HNSCC cell lines, supporting the presence of catalytically-independent and -dependent functions of SUV420H1. In a syngeneic mouse model of mouse oral carcinoma 1 tumors (MOC1),\n                  <jats:italic>Suv420h1<\/jats:italic>\n                  knockout (KO) in MOC1 cancer cells halted tumor growth and synergized with anti-PD-1 therapy. In the tumor immune microenvironment (TIME) of\n                  <jats:italic>Suv420h1<\/jats:italic>\n                  KO MOC1 tumors, a significant increase in the macrophage compartment with a concurrent decrease in the protumorigenic granulocytic myeloid derived suppressor cells (gMDSCs) was observed. Genome-wide mapping of SUV420H1-mediated H4K20me3 revealed enrichment of EMT-, IFN-response, and myeloid-attracting chemokines. This work provides rationale for the depletion\/degradation of SUV420H1 as a novel therapeutic strategy to hinder proliferation and invasion, and to impart sensitization to anti-PD-1 immunotherapy for patients with HPV-negative HNSCC tumors with\n                  <jats:italic>SUV420H1<\/jats:italic>\n                  gain\/amplification.\n                <\/jats:p>","DOI":"10.1101\/2025.10.20.683419","type":"posted-content","created":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T03:35:20Z","timestamp":1761017720000},"source":"Crossref","is-referenced-by-count":1,"title":["Oncogenic and immunomodulatory functions of SUV420H1 in HPV-negative head and neck squamous cell carcinoma"],"prefix":"10.64898","author":[{"given":"Arfa","family":"Moshiri","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Luff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sohyoung","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meiye","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohd Saleem","family":"Dar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malhar","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"McKinnon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elijah F.","family":"Edmondson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jawad","family":"Akhtar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vassiliki","family":"Saloura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025102308550943000_2025.10.20.683419v1.1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21820"},{"key":"2025102308550943000_2025.10.20.683419v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.semradonc.2011.12.004"},{"key":"2025102308550943000_2025.10.20.683419v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)32591-7"},{"issue":"16","key":"2025102308550943000_2025.10.20.683419v1.4","doi-asserted-by":"crossref","first-page":"2872","DOI":"10.1016\/j.molcel.2023.07.020","article-title":"Catalytic and non-catalytic mechanisms of histone H4 lysine 20 methyltransferase SUV420H1","volume":"83","year":"2023","journal-title":"Mol Cell"},{"key":"2025102308550943000_2025.10.20.683419v1.5","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200703081"},{"key":"2025102308550943000_2025.10.20.683419v1.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2019.06.021"},{"key":"2025102308550943000_2025.10.20.683419v1.7","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.2282"},{"key":"2025102308550943000_2025.10.20.683419v1.8","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1235"},{"key":"2025102308550943000_2025.10.20.683419v1.9","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt012"},{"key":"2025102308550943000_2025.10.20.683419v1.10","doi-asserted-by":"crossref","unstructured":"Lopez V , Tejedor JR , Carella A , Garcia MG , Santamarina-Ojeda P , Perez RF , et al. 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