{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T08:04:26Z","timestamp":1777363466868,"version":"3.51.4"},"reference-count":39,"publisher":"Elsevier BV","issue":"5","license":[{"start":{"date-parts":[[2020,9,1]],"date-time":"2020-09-01T00:00:00Z","timestamp":1598918400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,9,1]],"date-time":"2020-09-01T00:00:00Z","timestamp":1598918400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2020,8,20]],"date-time":"2020-08-20T00:00:00Z","timestamp":1597881600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Andr\u00e9 Fitsche and Fabiola Putrek"}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Immunobiology"],"published-print":{"date-parts":[[2020,9]]},"DOI":"10.1016\/j.imbio.2020.152009","type":"journal-article","created":{"date-parts":[[2020,8,21]],"date-time":"2020-08-21T11:02:41Z","timestamp":1598007761000},"page":"152009","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":26,"title":["The role of macrophages type 2 and T-regs in immune checkpoint inhibitor related adverse events"],"prefix":"10.1016","volume":"225","author":[{"given":"Daniela","family":"Mihic-Probst","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Reinehr","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susanne","family":"Dettwiler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabel","family":"Kolm","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Britschgi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ken","family":"Kudura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ewerton Marques","family":"Maggio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Lenggenhager","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisabeth J","family":"Rushing","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"issue":"7","key":"10.1016\/j.imbio.2020.152009_bib0005","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0160221","article-title":"Adverse events associated with immune checkpoint blockade in patients with Cancer: a systematic review of case reports","volume":"11","author":"Abdel-Wahab","year":"2016","journal-title":"PLoS One"},{"issue":"1","key":"10.1016\/j.imbio.2020.152009_bib0010","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1136\/jmedgenet-2018-105485","article-title":"Haemophagocytic lymphohistiocytosis complicating pembrolizumab treatment for metastatic breast cancer in a patient with the PRF1A91V gene polymorphism","volume":"56","author":"Al-Samkari","year":"2019","journal-title":"J. Med. Genet."},{"issue":"17","key":"10.1016\/j.imbio.2020.152009_bib0015","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1056\/NEJMoa1507643","article-title":"Nivolumab versus Docetaxel in advanced nonsquamous non-small-Cell lung Cancer","volume":"373","author":"Borghaei","year":"2015","journal-title":"N. Engl. J. Med."},{"issue":"2","key":"10.1016\/j.imbio.2020.152009_bib0020","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1056\/NEJMoa1504627","article-title":"Nivolumab versus Docetaxel in advanced squamous-cell non-small-Cell lung Cancer","volume":"373","author":"Brahmer","year":"2015","journal-title":"N. Engl. J. Med."},{"issue":"9","key":"10.1016\/j.imbio.2020.152009_bib0025","doi-asserted-by":"crossref","first-page":"3377","DOI":"10.1172\/JCI80012","article-title":"Cytotoxic T lymphocyte antigen-4 and immune checkpoint blockade","volume":"125","author":"Buchbinder","year":"2015","journal-title":"J. Clin. Invest."},{"issue":"12","key":"10.1016\/j.imbio.2020.152009_bib0030","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1038\/nri2889","article-title":"Mechanisms of impaired regulation by CD4(+)CD25(+)FOXP3(+) regulatory T cells in human autoimmune diseases","volume":"10","author":"Buckner","year":"2010","journal-title":"Nat. Rev. Immunol."},{"issue":"5","key":"10.1016\/j.imbio.2020.152009_bib0035","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1210\/er.2004-0011","article-title":"Autoimmune hypophysitis","volume":"26","author":"Caturegli","year":"2005","journal-title":"Endocr. Rev."},{"issue":"12","key":"10.1016\/j.imbio.2020.152009_bib0040","doi-asserted-by":"crossref","first-page":"3225","DOI":"10.1016\/j.ajpath.2016.08.020","article-title":"Hypophysitis secondary to cytotoxic T-Lymphocyte-Associated protein 4 blockade: insights into pathogenesis from an autopsy series","volume":"186","author":"Caturegli","year":"2016","journal-title":"Am. J. Pathol."},{"issue":"17","key":"10.1016\/j.imbio.2020.152009_bib0045","doi-asserted-by":"crossref","first-page":"3229","DOI":"10.1002\/cncr.30826","article-title":"A consensus review on malignancy-associated hemophagocytic lymphohistiocytosis in adults","volume":"123","author":"Daver","year":"2017","journal-title":"Cancer"},{"issue":"4","key":"10.1016\/j.imbio.2020.152009_bib0050","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1158\/2326-6066.CIR-16-0237","article-title":"Comprehensive meta-analysis of key immune-related adverse events from CTLA-4 and PD-1\/PD-L1 inhibitors in Cancer patients","volume":"5","author":"De Velasco","year":"2017","journal-title":"Cancer Immunol. Res."},{"issue":"1","key":"10.1016\/j.imbio.2020.152009_bib0055","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1186\/s13045-018-0637-x","article-title":"Immune cell subset differentiation and tissue inflammation","volume":"11","author":"Fang","year":"2018","journal-title":"J. Hematol. Oncol."},{"key":"10.1016\/j.imbio.2020.152009_bib0060","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.oraloncology.2018.04.008","article-title":"Nivolumab vs investigator\u2019s choice in recurrent or metastatic squamous cell carcinoma of the head and neck: 2-year long-term survival update of CheckMate 141 with analyses by tumor PD-L1 expression","volume":"81","author":"Ferris","year":"2018","journal-title":"Oral Oncol."},{"issue":"7655","key":"10.1016\/j.imbio.2020.152009_bib0065","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1038\/nature22396","article-title":"PD-1 expression by tumour-associated macrophages inhibits phagocytosis and tumour immunity","volume":"545","author":"Gordon","year":"2017","journal-title":"Nature"},{"issue":"1","key":"10.1016\/j.imbio.2020.152009_bib0070","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1186\/s40425-018-0384-0","article-title":"Severe hemophagocytic lymphohistiocytosis in a melanoma patient treated with ipilimumab + nivolumab","volume":"6","author":"Hantel","year":"2018","journal-title":"J. Immunother. Cancer"},{"issue":"15","key":"10.1016\/j.imbio.2020.152009_bib0075","doi-asserted-by":"crossref","first-page":"6303","DOI":"10.1073\/pnas.0809422106","article-title":"PD-1 expression by macrophages plays a pathologic role in altering microbial clearance and the innate inflammatory response to sepsis","volume":"106","author":"Huang","year":"2009","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"issue":"230","key":"10.1016\/j.imbio.2020.152009_bib0080","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.3008002","article-title":"Pituitary expression of CTLA-4 mediates hypophysitis secondary to administration of CTLA-4 blocking antibody","volume":"6","author":"Iwama","year":"2014","journal-title":"Sci. Transl. Med."},{"issue":"3","key":"10.1016\/j.imbio.2020.152009_bib0085","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1111\/imm.12788","article-title":"PD-1\/PD-L1 inhibitors in haematological malignancies: update 2017","volume":"152","author":"Jelinek","year":"2017","journal-title":"Immunology"},{"issue":"5","key":"10.1016\/j.imbio.2020.152009_bib0090","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1053\/j.seminoncol.2010.09.003","article-title":"Update on immunologic therapy with anti-CTLA-4 antibodies in melanoma: identification of clinical and biological response patterns, immune-related adverse events, and their management","volume":"37","author":"Kaehler","year":"2010","journal-title":"Semin. Oncol."},{"key":"10.1016\/j.imbio.2020.152009_bib0095","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s41199-020-0050-3","article-title":"Pembrolizumab-induced Hemophagocytic Lymphohistiocytosis: an immunotherapeutic challenge","volume":"5","author":"Kalmuk","year":"2020","journal-title":"Cancers Head Neck"},{"issue":"10","key":"10.1016\/j.imbio.2020.152009_bib0100","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.1016\/S1470-2045(16)30364-3","article-title":"Avelumab in patients with chemotherapy-refractory metastatic Merkel cell carcinoma: a multicentre, single-group, open-label, phase 2 trial","volume":"17","author":"Kaufman","year":"2016","journal-title":"Lancet Oncol."},{"issue":"1","key":"10.1016\/j.imbio.2020.152009_bib0105","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1056\/NEJMoa1504030","article-title":"Combined nivolumab and ipilimumab or monotherapy in untreated melanoma","volume":"373","author":"Larkin","year":"2015","journal-title":"N. Engl. J. Med."},{"issue":"13","key":"10.1016\/j.imbio.2020.152009_bib0110","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.1056\/NEJMc1509660","article-title":"Combined nivolumab and ipilimumab or monotherapy in untreated melanoma","volume":"373","author":"Larkin","year":"2015","journal-title":"N. Engl. J. Med."},{"issue":"16","key":"10.1016\/j.imbio.2020.152009_bib0115","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1056\/NEJMoa1910836","article-title":"Five-year survival with combined nivolumab and ipilimumab in advanced melanoma","volume":"381","author":"Larkin","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.imbio.2020.152009_bib0120","doi-asserted-by":"crossref","first-page":"13","DOI":"10.12703\/P6-13","article-title":"The M1 and M2 paradigm of macrophage activation: time for reassessment","volume":"6","author":"Martinez","year":"2014","journal-title":"F1000Prime Rep."},{"issue":"19","key":"10.1016\/j.imbio.2020.152009_bib0125","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1056\/NEJMoa1510665","article-title":"Nivolumab versus everolimus in advanced renal-cell carcinoma","volume":"373","author":"Motzer","year":"2015","journal-title":"N. Engl. J. Med."},{"issue":"1","key":"10.1016\/j.imbio.2020.152009_bib0130","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1182\/blood-2002-06-1668","article-title":"CTLA-4 is not restricted to the lymphoid cell lineage and can function as a target molecule for apoptosis induction of leukemic cells","volume":"101","author":"Pistillo","year":"2003","journal-title":"Blood"},{"issue":"19","key":"10.1016\/j.imbio.2020.152009_bib0135","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1056\/NEJMoa1606774","article-title":"Pembrolizumab versus chemotherapy for PD-L1-Positive non-small-Cell lung Cancer","volume":"375","author":"Reck","year":"2016","journal-title":"N. Engl. J. Med."},{"issue":"26","key":"10.1016\/j.imbio.2020.152009_bib0140","doi-asserted-by":"crossref","first-page":"2521","DOI":"10.1056\/NEJMoa1503093","article-title":"Pembrolizumab versus ipilimumab in advanced melanoma","volume":"372","author":"Robert","year":"2015","journal-title":"N. Engl. J. Med."},{"issue":"19","key":"10.1016\/j.imbio.2020.152009_bib0145","doi-asserted-by":"crossref","first-page":"6140","DOI":"10.1073\/pnas.1417320112","article-title":"Ipilimumab-dependent cell-mediated cytotoxicity of regulatory T cells ex vivo by nonclassical monocytes in melanoma patients","volume":"112","author":"Romano","year":"2015","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"issue":"10031","key":"10.1016\/j.imbio.2020.152009_bib0150","doi-asserted-by":"crossref","first-page":"1909","DOI":"10.1016\/S0140-6736(16)00561-4","article-title":"Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial","volume":"387","author":"Rosenberg","year":"2016","journal-title":"Lancet"},{"issue":"1","key":"10.1016\/j.imbio.2020.152009_bib0155","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1186\/s40425-018-0365-3","article-title":"Hemophagocytic lymphohistiocytosis with immunotherapy: brief review and case report","volume":"6","author":"Sadaat","year":"2018","journal-title":"J. Immunother. Cancer"},{"issue":"4","key":"10.1016\/j.imbio.2020.152009_bib0160","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1200\/JCO.2005.01.128","article-title":"Autoimmunity in a phase I trial of a fully human anti-cytotoxic T-lymphocyte antigen-4 monoclonal antibody with multiple melanoma peptides and Montanide ISA 51 for patients with resected stages III and IV melanoma","volume":"23","author":"Sanderson","year":"2005","journal-title":"J. Clin. Oncol."},{"issue":"6","key":"10.1016\/j.imbio.2020.152009_bib0165","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1016\/j.ejca.2006.01.003","article-title":"Tumour-associated macrophages are a distinct M2 polarised population promoting tumour progression: potential targets of anti-cancer therapy","volume":"42","author":"Sica","year":"2006","journal-title":"Eur. J. Cancer"},{"issue":"9","key":"10.1016\/j.imbio.2020.152009_bib0170","doi-asserted-by":"crossref","first-page":"1883","DOI":"10.1084\/jem.20091233","article-title":"Disordered macrophage cytokine secretion underlies impaired acute inflammation and bacterial clearance in Crohn\u2019s disease","volume":"206","author":"Smith","year":"2009","journal-title":"J. Exp. Med."},{"issue":"3","key":"10.1016\/j.imbio.2020.152009_bib0175","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1016\/j.immuni.2018.03.014","article-title":"Regulation and function of the PD-L1 checkpoint","volume":"48","author":"Sun","year":"2018","journal-title":"Immunity"},{"issue":"22","key":"10.1016\/j.imbio.2020.152009_bib0180","doi-asserted-by":"crossref","first-page":"5155","DOI":"10.1182\/blood-2011-11-388918","article-title":"Basis of CTLA-4 function in regulatory and conventional CD4(+) T cells","volume":"119","author":"Tai","year":"2012","journal-title":"Blood"},{"issue":"2","key":"10.1016\/j.imbio.2020.152009_bib0185","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1182\/blood-2009-08-236711","article-title":"Alternative activation of macrophages by IL-4 impairs phagocytosis of pathogens but potentiates microbial-induced signalling and cytokine secretion","volume":"115","author":"Varin","year":"2010","journal-title":"Blood"},{"issue":"1","key":"10.1016\/j.imbio.2020.152009_bib0190","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1046\/j.0300-9475.2001.01019.x","article-title":"Expression of CTLA-4 by human monocytes","volume":"55","author":"Wang","year":"2002","journal-title":"Scand. J. Immunol."},{"issue":"7","key":"10.1016\/j.imbio.2020.152009_bib0195","doi-asserted-by":"crossref","first-page":"638","DOI":"10.3109\/08820139.2014.909456","article-title":"Disequilibrium of M1 and M2 macrophages correlates with the development of experimental inflammatory bowel diseases","volume":"43","author":"Zhu","year":"2014","journal-title":"Immunol. Invest."}],"container-title":["Immunobiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0171298520303594?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0171298520303594?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T16:47:21Z","timestamp":1759250841000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0171298520303594"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9]]},"references-count":39,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2020,9]]}},"alternative-id":["S0171298520303594"],"URL":"https:\/\/doi.org\/10.1016\/j.imbio.2020.152009","relation":{},"ISSN":["0171-2985"],"issn-type":[{"value":"0171-2985","type":"print"}],"subject":[],"published":{"date-parts":[[2020,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"The role of macrophages type 2 and T-regs in immune checkpoint inhibitor related adverse events","name":"articletitle","label":"Article Title"},{"value":"Immunobiology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.imbio.2020.152009","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 The Authors. Published by Elsevier GmbH.","name":"copyright","label":"Copyright"}],"article-number":"152009"}}