{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T13:46:47Z","timestamp":1789739207828,"version":"4.0.1"},"reference-count":14,"publisher":"American Society for Clinical Investigation","issue":"4","license":[{"start":{"date-parts":[[2025,2,24]],"date-time":"2025-02-24T00:00:00Z","timestamp":1740355200000},"content-version":"vor","delay-in-days":48,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Duke Cancer Institute Pilot Award, Center for Prostate and Urologic Cancers, Duke University Medical Center","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,2,24]]},"abstract":"<jats:p>\n                    Since multiple front-line immune checkpoint inhibitor\u2013based (ICI-based) combinations are approved for metastatic renal cell carcinoma, biomarkers predicting for ICI responses are needed past clinical prognostication scores and transcriptome gene expression profiling. Circulating markers represent opportunities to assess baseline and dynamic changes in immune cell frequency and cytokine levels while on treatment. We conducted an exploratory prospective correlative study of 33 patients with metastatic clear cell renal cell carcinoma undergoing treatment with ICIs and correlated changes in circulating immune cell subsets and cytokines with clinical responses to treatment. Cell frequencies and cytokine levels were compared between responders and nonresponders using unpaired parametric t tests, using prespecified alpha level of significance of 0.05. Classical monocyte subsets (CD14\n                    <jats:sup>+<\/jats:sup>\n                    CD16\n                    <jats:sup>\u2013<\/jats:sup>\n                    ), as well as 7 cytokines (IL-12\/23 p40, macrophage inflammatory protein-1a, macrophage inflammatory protein-1b, vascular cell adhesion molecule-1, intercellular adhesion molecule-1, IL-8, and TNF-\u03b1) were higher at baseline for responding versus nonresponding patients. Dynamic changes in thymus- and activation-regulated chemokine (TARC), placental growth factor (PlGF), and vascular endothelial growth factor (VEGF) also correlated with patients with ICI response. In summary, macrophage-activating agents were observed to be important in ICI response and may highlight the importance of the innate immune response in ICI responses.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.185963","type":"journal-article","created":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T13:23:31Z","timestamp":1736256211000},"source":"Crossref","is-referenced-by-count":7,"title":["Circulating immune biomarkers correlating with response in patients with metastatic renal cell carcinoma on immunotherapy"],"prefix":"10.1172","volume":"10","author":[{"given":"Joyce","family":"Hwang","sequence":"first","affiliation":[{"name":"Division of Medical Oncology, Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eda","family":"Holl","sequence":"additional","affiliation":[{"name":"Department of Surgery, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Duke University, Durham, North Carolina, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anika","family":"Agarwal","sequence":"additional","affiliation":[{"name":"The University of North Carolina System, Chapel Hill, North Carolina, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark D.","family":"Starr","sequence":"additional","affiliation":[{"name":"Duke Cancer Institute Center for Prostate and Urologic Cancers, Durham, North Carolina, USA."},{"name":"Division of Medical Oncology, Department of Medicine, Duke University, Durham, North Carolina, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco A.","family":"Reyes Martinez","sequence":"additional","affiliation":[{"name":"Duke Cancer Institute Center for Prostate and Urologic Cancers, Durham, North Carolina, USA."},{"name":"Division of Medical Oncology, Department of Medicine, Duke University, Durham, North Carolina, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew Z.","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7012-1754","authenticated-orcid":true,"given":"Andrew J.","family":"Armstrong","sequence":"additional","affiliation":[{"name":"Duke Cancer Institute Center for Prostate and Urologic Cancers, Durham, North Carolina, USA."},{"name":"Division of Medical Oncology, Department of Medicine, Duke University, Durham, North Carolina, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Harrison","sequence":"additional","affiliation":[{"name":"Duke Cancer Institute Center for Prostate and Urologic Cancers, Durham, North Carolina, USA."},{"name":"Division of Medical Oncology, Department of Medicine, Duke University, Durham, North Carolina, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"George","sequence":"additional","affiliation":[{"name":"Duke Cancer Institute Center for Prostate and Urologic Cancers, Durham, North Carolina, USA."},{"name":"Division of Medical Oncology, Department of Medicine, Duke University, Durham, North Carolina, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew B.","family":"Nixon","sequence":"additional","affiliation":[{"name":"Duke Cancer Institute Center for Prostate and Urologic Cancers, Durham, North Carolina, USA."},{"name":"Division of Medical Oncology, Department of Medicine, Duke University, Durham, North Carolina, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Department of Internal Medicine, University of Texas, Southwestern Medical Center, Harold C. Simmons Comprehensive Cancer Center, Dallas, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2025,1,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21763"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctarc.2020.100183"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0053-3"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2020.10.011"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-1044-8"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2021-004316"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4466"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1136\/jclinpath-2014-202735"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01178"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-015-1714-4"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-009-9299-3"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2020-002009"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-20-2891"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2020-001460"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/185963\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T20:27:02Z","timestamp":1779136022000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/185963"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,7]]},"references-count":14,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,1,7]]},"published-print":{"date-parts":[[2025,2,24]]}},"alternative-id":["10.1172\/jci.insight.185963"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.185963","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,7]]},"article-number":"e185963"}}