{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T15:20:12Z","timestamp":1791300012431,"version":"4.1.0"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2013,4,1]],"date-time":"2013-04-01T00:00:00Z","timestamp":1364774400000},"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":[[2013,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>In this study, we assessed the involvement of IL-1\u03b2 in early angiogenic responses induced by malignant cells using Matrigel plugs supplemented with B16 melanoma cells. We found that during the angiogenic response, IL-1\u03b2 and vascular endothelial growth factor (VEGF) interact in a newly described autoinduction circuit, in which each of these cytokines induces the other. The IL-1\u03b2 and VEGF circuit acts through interactions between bone marrow\u2013derived VEGF receptor 1+\/IL-1R1+ immature myeloid cells and tissue endothelial cells. Myeloid cells produce IL-1\u03b2 and additional proinflammatory cytokines, which subsequently activate endothelial cells to produce VEGF and other proangiogenic factors and provide the inflammatory microenvironment for angiogenesis and tumor progression. These mechanisms were also observed in a nontumor early angiogenic response elicited in Matrigel plugs by either rIL-1\u03b2 or recombinant VEGF. We have shown that IL-1\u03b2 inhibition stably reduces tumor growth by limiting inflammation and inducing the maturation of immature myeloid cells into M1 macrophages. In sharp contrast, only transient inhibition of tumor growth was observed after VEGF neutralization, followed by tumor recurrence mediated by rebound angiogenesis. This occurs via the reprogramming of VEGF receptor 1+\/IL-1R1+ cells to express hypoxia inducible factor-1\u03b1, VEGF, and other angiogenic factors, thereby directly supporting proliferation of endothelial cells and blood vessel formation in a paracrine manner. We suggest using IL-1\u03b2 inhibition as an effective antitumor therapy and are currently optimizing the conditions for its application in the clinic.<\/jats:p>","DOI":"10.4049\/jimmunol.1202769","type":"journal-article","created":{"date-parts":[[2013,3,8]],"date-time":"2013-03-08T23:09:18Z","timestamp":1362784158000},"page":"3500-3509","source":"Crossref","is-referenced-by-count":194,"title":["The Role of IL-1\u03b2 in the Early Tumor Cell\u2013Induced Angiogenic Response"],"prefix":"10.1093","volume":"190","author":[{"given":"Yaron","family":"Carmi","sequence":"first","affiliation":[{"name":"The Shraga Segal Department of Microbiology, Immunology and Genetics and The Cancer Research Center, Faculty of Health Sciences, Ben-Gurion University of the Negev , Beer-Sheva 84105,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahar","family":"Dotan","sequence":"additional","affiliation":[{"name":"The Shraga Segal Department of Microbiology, Immunology and Genetics and The Cancer Research Center, Faculty of Health Sciences, Ben-Gurion University of the Negev , Beer-Sheva 84105,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peleg","family":"Rider","sequence":"additional","affiliation":[{"name":"The Shraga Segal Department of Microbiology, Immunology and Genetics and The Cancer Research Center, Faculty of Health Sciences, Ben-Gurion University of the Negev , Beer-Sheva 84105,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irena","family":"Kaplanov","sequence":"additional","affiliation":[{"name":"The Shraga Segal Department of Microbiology, Immunology and Genetics and The Cancer Research Center, Faculty of Health Sciences, Ben-Gurion University of the Negev , Beer-Sheva 84105,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malka R","family":"White","sequence":"additional","affiliation":[{"name":"The Shraga Segal Department of Microbiology, Immunology and Genetics and The Cancer Research Center, Faculty of Health Sciences, Ben-Gurion University of the Negev , Beer-Sheva 84105,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rona","family":"Baron","sequence":"additional","affiliation":[{"name":"The Shraga Segal Department of Microbiology, Immunology and Genetics and The Cancer Research Center, Faculty of Health Sciences, Ben-Gurion University of the Negev , Beer-Sheva 84105,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shai","family":"Abutbul","sequence":"additional","affiliation":[{"name":"The Shraga Segal Department of Microbiology, Immunology and Genetics and The Cancer Research Center, Faculty of Health Sciences, Ben-Gurion University of the Negev , Beer-Sheva 84105,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Huszar","sequence":"additional","affiliation":[{"name":"Pathology Department, Kaplan Medical Center , Rehovot 76100,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles A","family":"Dinarello","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Colorado , Denver, Aurora, CO 80045"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ron N","family":"Apte","sequence":"additional","affiliation":[{"name":"The Shraga Segal Department of Microbiology, Immunology and Genetics and The Cancer Research Center, Faculty of Health Sciences, Ben-Gurion University of the Negev , Beer-Sheva 84105,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Voronov","sequence":"additional","affiliation":[{"name":"The Shraga Segal Department of Microbiology, Immunology and Genetics and The Cancer Research Center, Faculty of Health Sciences, Ben-Gurion University of the Negev , Beer-Sheva 84105,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,4,1]]},"reference":[{"key":"2025032406500995300_r1","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1111\/j.1600-065X.2008.00615.x","article-title":"Is interleukin-1 a good or bad \u2018guy\u2019 in tumor immunobiology and immunotherapy?","volume":"222","author":"Apte","year":"2008","journal-title":"Immunol. 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