{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T11:54:26Z","timestamp":1791028466640,"version":"4.1.0"},"reference-count":39,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T00:00:00Z","timestamp":1790985600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T00:00:00Z","timestamp":1790985600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30 CA006973"],"award-info":[{"award-number":["P30 CA006973"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Oncology"],"abstract":"<jats:p>\n                    Adoptive transfer of proinflammatory myeloid cells enhances antitumor T\u2010cell responses and limits tumor growth in murine models. Previous work identified transcription factors NF\u2010\u03baB p50 and STAT6 as key regulators whose inactivation enhances the inflammatory potential of murine myeloid cells. Herein, we translate murine findings to human cells and establish methods to generate proinflammatory myeloid cells from human marrow\u2010derived CD34\n                    <jats:sup>+<\/jats:sup>\n                    hematopoietic stem and progenitor cells (HSPCs). Using CRISPR\u2010Cas9, we disrupted\n                    <jats:italic>NFKB1<\/jats:italic>\n                    ,\n                    <jats:italic>STAT6<\/jats:italic>\n                    , both\n                    <jats:italic>NFKB1<\/jats:italic>\n                    and\n                    <jats:italic>STAT6<\/jats:italic>\n                    , or\n                    <jats:italic>NFKB1<\/jats:italic>\n                    and\n                    <jats:italic>NFKB2<\/jats:italic>\n                    (encoding NF\u2010\u03baB p52), achieving robust loss of target proteins. We determined conditions for expanding HSPCs and differentiating them into monocytes. To evaluate proinflammatory potential under immune\u2010suppressive conditions, edited monocytes were differentiated into macrophages, exposed to IL\u20104, and analyzed for gene expression. RNA sequencing revealed enhanced proinflammatory pathway activation in STAT6\u2010 and p50\/STAT6\u2010deficient macrophages, but not in p50\u2010 or p50\/p52\u2010deficient macrophages. Transcriptomic analysis was validated by measuring protein secretion of a subset of inflammatory mediators. These findings establish a strategy to generate proinflammatory human myeloid cells with potential clinical application in cancer immunotherapy. Future clinical evaluation will be required to determine whether STAT6\u2010IMC or p50\/STAT6\u2010IMC exhibit superior therapeutic efficacy.\n                  <\/jats:p>","DOI":"10.1002\/1878-0261.70346","type":"journal-article","created":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T11:21:31Z","timestamp":1791026491000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Engineering\n                    <scp>IL<\/scp>\n                    \u20104 resistant proinflammatory human myeloid cells for cancer immunotherapy"],"prefix":"10.1002","author":[{"given":"Theresa","family":"Barberi","sequence":"first","affiliation":[{"name":"Department of Oncology Johns Hopkins University  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5615-7061","authenticated-orcid":false,"given":"Alan D.","family":"Friedman","sequence":"additional","affiliation":[{"name":"Department of Oncology Johns Hopkins University  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,3]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1172\/JCI31422","article-title":"Altered macrophage differentiation and immune dysfunction in tumor development","volume":"117","author":"Sica A","year":"2007","journal-title":"J Clin Invest"},{"key":"e_1_2_11_3_1","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.immuni.2014.06.010","article-title":"Tumor\u2010associated macrophages: from mechanisms to therapy","volume":"41","author":"Noy R","year":"2014","journal-title":"Immunity"},{"key":"e_1_2_11_4_1","doi-asserted-by":"crossref","DOI":"10.1038\/s41392-025-02325-5","article-title":"Dual roles and therapeutic targeting of tumor\u2010associated macrophages in tumor 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