{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T20:01:09Z","timestamp":1784145669677,"version":"3.55.0"},"reference-count":46,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"657","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2022,8,10]]},"abstract":"<jats:p>\n            Upon chronic antigen exposure, CD8\n            <jats:sup>+<\/jats:sup>\n            T cells become exhausted, acquiring a dysfunctional state correlated with the inability to control infection or tumor progression. In contrast, stem-like CD8\n            <jats:sup>+<\/jats:sup>\n            T progenitors maintain the ability to promote and sustain effective immunity. Adenovirus (Ad)\u2013vectored vaccines encoding tumor neoantigens have been shown to eradicate large tumors when combined with anti\u2013programmed cell death protein 1 (\u03b1PD-1) in murine models; however, the mechanisms and translational potential have not yet been elucidated. Here, we show that gorilla Ad vaccine targeting tumor neoepitopes enhances responses to \u03b1PD-1 therapy by improving immunogenicity and antitumor efficacy. Single-cell RNA sequencing demonstrated that the combination of Ad vaccine and \u03b1PD-1 increased the number of murine polyfunctional neoantigen-specific CD8\n            <jats:sup>+<\/jats:sup>\n            T cells over \u03b1PD-1 monotherapy, with an accumulation of Tcf1\n            <jats:sup>+<\/jats:sup>\n            stem-like progenitors in draining lymph nodes and effector CD8\n            <jats:sup>+<\/jats:sup>\n            T cells in tumors. Combined T cell receptor (TCR) sequencing analysis highlighted a broader spectrum of neoantigen-specific CD8\n            <jats:sup>+<\/jats:sup>\n            T cells upon vaccination compared to \u03b1PD-1 monotherapy. The translational relevance of these data is supported by results obtained in the first 12 patients with metastatic deficient mismatch repair (dMMR) tumors vaccinated with an Ad vaccine encoding shared neoantigens. Expansion and diversification of TCRs were observed in post-treatment biopsies of patients with clinical response, as well as an increase in tumor-infiltrating T cells with an effector memory signature. These findings indicate a promising mechanism to overcome resistance to PD-1 blockade by promoting immunogenicity and broadening the spectrum and magnitude of neoantigen-specific T cells infiltrating tumors.\n          <\/jats:p>","DOI":"10.1126\/scitranslmed.abo7604","type":"journal-article","created":{"date-parts":[[2022,8,10]],"date-time":"2022-08-10T17:58:13Z","timestamp":1660154293000},"source":"Crossref","is-referenced-by-count":67,"title":["Adenoviral-based vaccine promotes neoantigen-specific CD8\n            <sup>+<\/sup>\n            T cell stemness and tumor rejection"],"prefix":"10.1126","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0763-6269","authenticated-orcid":true,"given":"Anna Morena","family":"D\u2019Alise","sequence":"first","affiliation":[{"name":"Nouscom SRL, 00128 Rome, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7008-3727","authenticated-orcid":true,"given":"Nadia","family":"Brasu","sequence":"additional","affiliation":[{"name":"Armenise-Harvard Immune Regulation Unit, Italian Institute for Genomic Medicine, 10060 Candiolo (Turin), Italy."},{"name":"Candiolo Cancer Institute, FPO- IRCCS, 10060 Candiolo (Turin), Italy."},{"name":"University of Turin, 10060 Turin, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6791-7126","authenticated-orcid":true,"given":"Carlo","family":"De Intinis","sequence":"additional","affiliation":[{"name":"Armenise-Harvard Immune Regulation Unit, Italian Institute for Genomic Medicine, 10060 Candiolo (Turin), Italy."},{"name":"Candiolo Cancer Institute, FPO- IRCCS, 10060 Candiolo (Turin), Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0502-1962","authenticated-orcid":true,"given":"Guido","family":"Leoni","sequence":"additional","affiliation":[{"name":"Nouscom SRL, 00128 Rome, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Russo","sequence":"additional","affiliation":[{"name":"Armenise-Harvard Immune Regulation Unit, Italian Institute for Genomic Medicine, 10060 Candiolo (Turin), Italy."},{"name":"Candiolo Cancer Institute, FPO- IRCCS, 10060 Candiolo (Turin), Italy."},{"name":"University of Turin, 10060 Turin, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3623-3004","authenticated-orcid":true,"given":"Francesca","family":"Langone","sequence":"additional","affiliation":[{"name":"Nouscom SRL, 00128 Rome, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denis","family":"Baev","sequence":"additional","affiliation":[{"name":"Armenise-Harvard Immune Regulation Unit, Italian Institute for Genomic Medicine, 10060 Candiolo (Turin), Italy."},{"name":"Candiolo Cancer Institute, FPO- IRCCS, 10060 Candiolo (Turin), Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1180-0359","authenticated-orcid":true,"given":"Elisa","family":"Micarelli","sequence":"additional","affiliation":[{"name":"Nouscom SRL, 00128 Rome, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Petiti","sequence":"additional","affiliation":[{"name":"Armenise-Harvard Immune Regulation Unit, Italian Institute for Genomic Medicine, 10060 Candiolo (Turin), Italy."},{"name":"Candiolo Cancer Institute, FPO- IRCCS, 10060 Candiolo (Turin), Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Picelli","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Clinical Ophthalmology Basel, 4031 Basel, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6554-5488","authenticated-orcid":true,"given":"Marwan","family":"Fakih","sequence":"additional","affiliation":[{"name":"City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dung T.","family":"Le","sequence":"additional","affiliation":[{"name":"Johns Hopkins University, Baltimore, MD 21287, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5377-135X","authenticated-orcid":true,"given":"Michael J.","family":"Overman","sequence":"additional","affiliation":[{"name":"MD Anderson Cancer Center (MDACC), Houston, TX 77030, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9122-1014","authenticated-orcid":true,"given":"Anthony F.","family":"Shields","sequence":"additional","affiliation":[{"name":"Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrina S.","family":"Pedersen","sequence":"additional","affiliation":[{"name":"Division of Oncology, Washington University School of Medicine, St. Louis, MO 63110, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6913-9655","authenticated-orcid":true,"given":"Manish A.","family":"Shah","sequence":"additional","affiliation":[{"name":"Weill Cornell Medicine, New York, NY 10021, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarbajit","family":"Mukherjee","sequence":"additional","affiliation":[{"name":"Roswell Park Comprehensive Cancer Center, Buffalo, 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