{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T11:22:38Z","timestamp":1790508158479,"version":"4.1.0"},"reference-count":34,"publisher":"American Society for Clinical Investigation","issue":"5","license":[{"start":{"date-parts":[[2022,3,8]],"date-time":"2022-03-08T00:00:00Z","timestamp":1646697600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["Intramural research program"],"award-info":[{"award-number":["Intramural research program"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,3,8]]},"abstract":"<jats:p>\n                    Therapeutic IL-12 has demonstrated the ability to reduce local immune suppression in preclinical models, but clinical development has been limited by severe inflammation-related adverse events with systemic administration. Here, we show that potent immunologic tumor control of established syngeneic carcinomas can be achieved by i.t. administration of a tumor-targeted IL-12 antibody fusion protein (NHS\u2013rmIL-12) using sufficiently low doses to avoid systemic toxicity. Single-cell transcriptomic analysis and ex vivo functional assays of NHS\u2013rmIL-12\u2013treated tumors revealed reinvigoration and enhanced proliferation of exhausted CD8\n                    <jats:sup>+<\/jats:sup>\n                    T lymphocytes, induction of Th1 immunity, and a decrease in Treg number and suppressive capacity. Similarly, myeloid cells transitioned toward inflammatory phenotypes and displayed reduced suppressive capacity. Cell type\u2013specific IL-12 receptor\u2013KO BM chimera studies revealed that therapeutic modulation of both lymphoid and myeloid cells is required for maximum treatment effect and tumor cure. Study of single-cell data sets from human head and neck carcinomas revealed IL-12 receptor expression patterns similar to those observed in murine tumors. These results describing the diverse mechanisms underlying tumor-directed IL-12\u2013induced antitumor immunity provide the preclinical rationale for the clinical study of i.t. NHS\u2013IL-12.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.157448","type":"journal-article","created":{"date-parts":[[2022,3,7]],"date-time":"2022-03-07T14:00:56Z","timestamp":1646661656000},"source":"Crossref","is-referenced-by-count":16,"title":["Cure of syngeneic carcinomas with targeted IL-12 through obligate reprogramming of lymphoid and myeloid immunity"],"prefix":"10.1172","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0981-2702","authenticated-orcid":true,"given":"Youji","family":"Hong","sequence":"first","affiliation":[{"name":"Section on Translational Tumor Immunology, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0940-3941","authenticated-orcid":true,"given":"Yvette","family":"Robbins","sequence":"additional","affiliation":[{"name":"Section on Translational Tumor Immunology, National Institute on 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