{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T19:59:34Z","timestamp":1788897574905,"version":"build-2803163510"},"reference-count":63,"publisher":"National Academy of Sciences","issue":"26","license":[{"start":{"date-parts":[[2022,6,24]],"date-time":"2022-06-24T00:00:00Z","timestamp":1656028800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"NIH","award":["INTRAMURAL PROGRAM"],"award-info":[{"award-number":["INTRAMURAL PROGRAM"]}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2022,6,28]]},"abstract":"<jats:p>\n                    Tumor infiltration by T cells profoundly affects cancer progression and responses to immunotherapy. However, the tumor immunosuppressive microenvironment can impair the induction, trafficking, and local activity of antitumor T cells. Here, we investigated whether intratumoral injection of virus-derived peptide epitopes could activate preexisting antiviral T cell responses locally and promote antitumor responses or antigen spreading. We focused on a mouse model of cytomegalovirus (CMV), a highly prevalent human infection that induces vigorous and durable T cell responses. Mice persistently infected with murine CMV (MCMV) were challenged with lung (TC-1), colon (MC-38), or melanoma (B16-F10) tumor cells. Intratumoral injection of MCMV-derived T cell epitopes triggered in situ and systemic expansion of their cognate, MCMV-specific CD4\n                    <jats:sup>+<\/jats:sup>\n                    or CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells. The MCMV CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell epitopes injected alone provoked arrest of tumor growth and some durable remissions. Intratumoral injection of MCMV CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell epitopes with polyinosinic acid:polycytidylic acid (pI:C) preferentially elicited tumor antigen\u2013specific CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells, promoted tumor clearance, and conferred long-term protection against tumor rechallenge. Notably, secondary proliferation of MCMV-specific CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells correlated with better tumor control. Importantly, intratumoral injection of MCMV-derived CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell\u2013peptide epitopes alone or CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell\u2013peptide epitopes with pI:C induced potent adaptive and innate immune activation of the tumor microenvironment. Thus, CMV-derived peptide epitopes, delivered intratumorally, act as cytotoxic and immunotherapeutic agents to promote immediate tumor control and long-term antitumor immunity that could be used as a stand-alone therapy. The tumor antigen\u2013agnostic nature of this approach makes it applicable across a broad range of solid tumors regardless of their origin.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2116738119","type":"journal-article","created":{"date-parts":[[2022,6,24]],"date-time":"2022-06-24T13:30:31Z","timestamp":1656077431000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":46,"title":["Harnessing anti-cytomegalovirus immunity for local immunotherapy against solid tumors"],"prefix":"10.1073","volume":"119","author":[{"given":"Nicolas","family":"\u00c7uburu","sequence":"first","affiliation":[{"name":"Laboratory of Cellular Oncology, National Cancer Institute, NIH, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukasz","family":"Bialkowski","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Oncology, National Cancer Institute, NIH, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7756-9831","authenticated-orcid":false,"given":"Sergio M.","family":"Pontejo","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiv K.","family":"Sethi","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Oncology, National Cancer Institute, NIH, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander T. F.","family":"Bell","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Oncology, National Cancer Institute, NIH, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rina","family":"Kim","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Oncology, National Cancer Institute, NIH, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia D.","family":"Thompson","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Oncology, National Cancer Institute, NIH, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas R.","family":"Lowy","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Oncology, National Cancer Institute, NIH, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John T.","family":"Schiller","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Oncology, National Cancer Institute, NIH, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2022,6,24]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.02.013"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms9683"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature22991"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature23003"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.10.028"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-20-0305"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-13-1923"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdx683"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-14-0024"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-17-1866"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.04.031"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aan4488"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2018.01.019"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2018.07.003"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.08.027"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-018-0014-6"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/rmv.2034"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2016.38"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20160758"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-08-518183"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djw261"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.1.450"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0308054101"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.09.076"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-17-0249"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2017.49"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20160801"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature14001"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2017.11.012"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1002\/rmv.655"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0130-2"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-08534-1"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1719-9"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1080\/21645515.2017.1331795"},{"key":"e_1_3_4_35_2","first-page":"21","article-title":"Treatment of established tumors with a novel vaccine that enhances major histocompatibility class II presentation of tumor antigen","volume":"56","author":"Lin K. 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