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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,3,17]]},"abstract":"<jats:p>\n                    The loss of major histocompatibility complex class I (MHC-I) molecules has been proposed as a mechanism for cancer immune evasion. Nevertheless, the mechanism is poorly understood. We report here that membrane-associated RING-CH-type finger 8 (MARCHF8), upregulated by human papillomavirus (HPV), ubiquitinates and degrades MHC-I in HPV-positive head and neck cancer (HPV+ HNC). Inhibiting MARCHF8 restores MHC-I levels on HPV+ HNC cells, suppresses tumor growth, and increases the infiltration of natural killer (NK) and T cells in the tumor microenvironment. Furthermore,\n                    <jats:italic toggle=\"yes\">Marchf8<\/jats:italic>\n                    knockout markedly increases cross talk between cytotoxic NK cells and CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells with macrophages and enhances the tumor-killing activity of CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells. Interestingly,\n                    <jats:italic toggle=\"yes\">Marchf8<\/jats:italic>\n                    knockout, in combination with anti-PD-1 treatment, further enhances tumor suppression and increases NK and T cell infiltration in mice bearing immune checkpoint inhibitor\u2013refractory tumors. Our findings suggest that MARCHF8 could be a promising target for immunotherapy for HPV+ HNC patients.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2525730123","type":"journal-article","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T19:00:41Z","timestamp":1773082841000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":2,"title":["The membrane-associated ubiquitin ligase MARCHF8 degrades MHC-I in HPV-positive head and neck cancer for immune evasion"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8331-1490","authenticated-orcid":false,"given":"Mohamed I.","family":"Khalil","sequence":"first","affiliation":[{"name":"Department of Microbiology, Genetics, and Immunology, Michigan State University","place":["East Lansing"]},{"name":"Department of Molecular Biology, National Research Centre","place":["Cairo, 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