{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T23:43:42Z","timestamp":1781826222893,"version":"3.54.5"},"posted":{"date-parts":[[2026,4,10]]},"group-title":"Cancer Biology","reference-count":0,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T00:00:00Z","timestamp":1775779200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"name":"Intramural Research Program of the Center for Cancer Research of the National Cancer Institute","award":["ZIA-BC010313, ZIA-BC010876, ZIA-BC010877, and ZIA-BC011870 to XWW; and ZIA-BC010891 and ZIC-BC011891 to MH"],"award-info":[{"award-number":["ZIA-BC010313, ZIA-BC010876, ZIA-BC010877, and ZIA-BC011870 to XWW; and ZIA-BC010891 and ZIC-BC011891 to MH"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,10]]},"abstract":"<jats:p>Cancer development is shaped by host-microbe interactions, including viral infections. While several viruses are established oncogenic drivers, their potential protective roles in cancer remain unclear. Here we identify a dominant antibody response to CE1, a consensus epitope of enterovirus and rhinovirus, that is associated with reduced hepatocellular carcinoma (HCC) incidence and mortality. Anti-CE1 antibodies selectively recognize HCC cells and mediate anti-tumor activity through NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC). Mechanistically, anti-CE1 antibodies cross-react with aspartate \u03b2-hydroxylase (ASPH), with CE1-ASPH sequence homology underpinning tumor recognition and cytotoxicity. Clinically, ASPH is aberrantly upregulated in HCC and correlates with inferred NK cell-associated ADCC activity and improved survival in CE1-seropositive patients. Collectively, these findings reveal a mechanism by which antiviral humoral immunity confers cancer protection through molecular mimicry and highlight anti-CE1 immunity as a potential therapeutic strategy in HCC.<\/jats:p>","DOI":"10.64898\/2026.04.07.717032","type":"posted-content","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T21:25:23Z","timestamp":1775856323000},"source":"Crossref","is-referenced-by-count":1,"title":["Enteroviral epitope mimicry enables NK cell-mediated targeting of ASPH in hepatocellular carcinoma"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7449-5857","authenticated-orcid":false,"given":"Man Hsin","family":"Hung","sequence":"first","affiliation":[{"name":"National Cancer Institute;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Li","sequence":"additional","affiliation":[{"name":"National Cancer Institute;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Limin","family":"Wang","sequence":"additional","affiliation":[{"name":"National Institutes of Health\/National Cancer Institute;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marshonna","family":"Forgues","sequence":"additional","affiliation":[{"name":"National Cancer Institute;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4441-8028","authenticated-orcid":false,"given":"Andrew S.","family":"Lee","sequence":"additional","affiliation":[{"name":"National Cancer Institute;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa M","family":"Jenkins","sequence":"additional","affiliation":[{"name":"National Cancer Institute;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tapan K.","family":"Maity","sequence":"additional","affiliation":[{"name":"National Cancer Institute;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesse","family":"Buffington","sequence":"additional","affiliation":[{"name":"National Cancer Institute;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jittiporn","family":"Chaisaingmongkol","sequence":"additional","affiliation":[{"name":"Chulabhorn Research Institute;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siritida","family":"Rabibhadana","sequence":"additional","affiliation":[{"name":"Chulabhorn Research Institute;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathuros","family":"Ruchirawat","sequence":"additional","affiliation":[{"name":"Chulabhorn Research Institute;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9152-5405","authenticated-orcid":false,"given":"Mitchell","family":"Ho","sequence":"additional","affiliation":[{"name":"National Cancer Institute, NIH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9735-606X","authenticated-orcid":false,"given":"Xin Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"National Cancer Institute;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.04.07.717032","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T21:25:23Z","timestamp":1775856323000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.04.07.717032"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,10]]},"references-count":0,"URL":"https:\/\/doi.org\/10.64898\/2026.04.07.717032","relation":{},"subject":[],"published":{"date-parts":[[2026,4,10]]},"subtype":"preprint"}}