{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T19:35:36Z","timestamp":1789932936662,"version":"4.0.1"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2016,3,1]],"date-time":"2016-03-01T00:00:00Z","timestamp":1456790400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The incidence of human papillomavirus (HPV)\u2013related head and neck squamous cell carcinoma has increased in recent decades, though HPV prevention vaccines may reduce this rise in the future. HPV-related cancers express the viral oncoproteins E6 and E7. The latter inactivates the tumor suppressor protein retinoblastoma (Rb), which leads to the overexpression of p16INK4 protein, providing unique Ags for therapeutic HPV-specific cancer vaccination. We developed potential adenoviral vaccines that express a fusion protein of HPV-16 E6 and E7 (Ad.E6E7) alone or fused with p16 (Ad.E6E7p16) and also encoding an anti\u2013programmed death (PD)-1 Ab. Human monocyte-derived dendritic cells (DC) transduced with Ad.E6E7 or Ad.E6E7p16 with or without Ad.\u03b1PD1 were used to activate autologous CD8 CTL in vitro. CTL responses were tested against naturally HPV-infected head and neck squamous cell carcinoma cells using IFN-\u03b3 ELISPOT and [51Cr]release assay. Surprisingly, stimulation and antitumor activity of CTL were increased after incubation with Ad.E6E7p16-transduced DC (DC.E6E7p16) compared with Ad.E6E7 (DC.E6E7), a result that may be due to an effect of p16 on cyclin-dependent kinase 4 levels and IL-12 secretion by DC. Moreover, the beneficial effect was most prominent when anti\u2013PD-1 was introduced during the second round of stimulation (after initial priming). These data suggest that careful sequencing of Ad.E6E7.p16 with Ad.\u03b1PD1 could improve antitumor immunity against HPV-related tumors and that p16 may enhance the immunogenicity of DC, through cyclin-dependent pathways, Th1 cytokine secretion, and by adding a nonviral Ag highly overexpressed in HPV-induced cancers.<\/jats:p>","DOI":"10.4049\/jimmunol.1502027","type":"journal-article","created":{"date-parts":[[2016,2,6]],"date-time":"2016-02-06T03:14:29Z","timestamp":1454728469000},"page":"2870-2878","source":"Crossref","is-referenced-by-count":20,"title":["Enhanced Cytotoxic CD8 T Cell Priming Using Dendritic Cell\u2013Expressing Human Papillomavirus-16 E6\/E7-p16INK4 Fusion Protein with Sequenced Anti\u2013Programmed Death-1"],"prefix":"10.1093","volume":"196","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7579-5272","authenticated-orcid":false,"given":"Tatiana M","family":"Garcia-Bates","sequence":"first","affiliation":[{"name":"Department of Otolaryngology, University of Pittsburgh , Pittsburgh, PA 15232"},{"name":"Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh , Pittsburgh, PA 15232"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Pittsburgh , Pittsburgh, PA 15232"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3079-1996","authenticated-orcid":false,"given":"Fernando","family":"Concha-Benavente","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Pittsburgh , Pittsburgh, PA 15232"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumita","family":"Trivedi","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, University of Pittsburgh , Pittsburgh, PA 15232"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robbie B","family":"Mailliard","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh , Pittsburgh, PA 15232"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Gambotto","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Pittsburgh , Pittsburgh, PA 15232"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert L","family":"Ferris","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, University of Pittsburgh , Pittsburgh, PA 15232"},{"name":"Department of Immunology, University of Pittsburgh , Pittsburgh, PA 15232"},{"name":"Cancer Immunology Program, University of Pittsburgh Cancer Institute , Pittsburgh, PA 15213"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2016,3,15]]},"reference":[{"key":"2025030702143400400_r1","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1200\/JCO.2007.14.1713","article-title":"Incidence trends for human papillomavirus-related and -unrelated oral squamous cell carcinomas in the United States","volume":"26","author":"Chaturvedi","year":"2008","journal-title":"J. Clin. Oncol."},{"key":"2025030702143400400_r2","doi-asserted-by":"crossref","first-page":"2620","DOI":"10.1002\/ijc.22177","article-title":"Human papillomavirus as a risk factor for the increase in incidence of tonsillar cancer","volume":"119","author":"Hammarstedt","year":"2006","journal-title":"Int. J. Cancer"},{"key":"2025030702143400400_r3","doi-asserted-by":"crossref","first-page":"4294","DOI":"10.1200\/JCO.2011.36.4596","article-title":"Human papillomavirus and rising oropharyngeal cancer incidence in the United States","volume":"29","author":"Chaturvedi","year":"2011","journal-title":"J. Clin. Oncol."},{"key":"2025030702143400400_r4","doi-asserted-by":"crossref","first-page":"665","DOI":"10.6004\/jnccn.2011.0055","article-title":"The epidemic of HPV-associated oropharyngeal cancer is here: is it time to change our treatment paradigms?","volume":"9","author":"Sturgis","year":"2011","journal-title":"J. Natl. Compr. Canc. 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