{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,9]],"date-time":"2026-11-09T12:30:40Z","timestamp":1794227440566,"version":"4.9.0"},"reference-count":41,"publisher":"Elsevier BV","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"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["RC18-2638151"],"award-info":[{"award-number":["RC18-2638151"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005010","name":"Associazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","award":["20353"],"award-info":[{"award-number":["20353"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005010","name":"Associazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","award":["IG 2017"],"award-info":[{"award-number":["IG 2017"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Pharmacological Research"],"published-print":{"date-parts":[[2020,9]]},"DOI":"10.1016\/j.phrs.2020.104957","type":"journal-article","created":{"date-parts":[[2020,5,30]],"date-time":"2020-05-30T11:25:32Z","timestamp":1590837932000},"page":"104957","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":35,"special_numbering":"C","title":["Targeting the vascular endothelial growth factor receptor-1 by the monoclonal antibody D16F7 to increase the activity of immune checkpoint inhibitors against cutaneous melanoma"],"prefix":"10.1016","volume":"159","author":[{"given":"Pedro Miguel","family":"Lacal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Grazia","family":"Atzori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Ruffini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Scimeca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Bonanno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosella","family":"Cicconi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Mattei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Bernardini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"D\u2019Atri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucio","family":"Tentori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grazia","family":"Graziani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.phrs.2020.104957_bib0005","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1056\/NEJMoa1709684","article-title":"Overall survival with combined nivolumab and ipilimumab in advanced melanoma","volume":"377","author":"Wolchok","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.phrs.2020.104957_bib0010","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1016\/S1470-2045(19)30388-2","article-title":"Pembrolizumab versus ipilimumab in advanced melanoma (KEYNOTE-006): post-hoc 5-year results from an open-label, multicentre, randomised, controlled, phase 3 study","volume":"20","author":"Robert","year":"2019","journal-title":"Lancet Oncol."},{"key":"10.1016\/j.phrs.2020.104957_bib0015","doi-asserted-by":"crossref","first-page":"1884","DOI":"10.1093\/annonc\/mdz411","article-title":"ESMO guidelines committee. Cutaneous melanoma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up","volume":"30","author":"Michielin","year":"2019","journal-title":"Ann. Oncol."},{"key":"10.1016\/j.phrs.2020.104957_bib0020","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.phrs.2020.104957_bib0025","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1186\/s40425-018-0355-5","article-title":"Immune oncology, immune responsiveness and the theory of everything","volume":"6","author":"Turan","year":"2018","journal-title":"J. Immunother. Cancer"},{"key":"10.1016\/j.phrs.2020.104957_bib0030","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1038\/s41591-019-0382-x","article-title":"Genomic correlates of response to immune checkpoint blockade","volume":"25","author":"Keenan","year":"2019","journal-title":"Nat. Med."},{"key":"10.1016\/j.phrs.2020.104957_bib0035","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.phrs.2018.08.023","article-title":"Therapeutic implication of vascular endothelial growth factor receptor-1 (VEGFR-1) targeting in cancer cells and tumor microenvironment by competitive and non-competitive inhibitors","volume":"136","author":"Lacal","year":"2018","journal-title":"Pharmacol. Res."},{"key":"10.1016\/j.phrs.2020.104957_bib0040","doi-asserted-by":"crossref","DOI":"10.3390\/ijms21041388","article-title":"Role of VEGFs\/VEGFR-1 signaling and its inhibition in modulating tumor invasion: experimental evidence in different metastatic Cancer models","volume":"21","author":"Ceci","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.phrs.2020.104957_bib0045","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1007\/s10555-011-9281-4","article-title":"Angiogenesis and immunity: a bidirectional link potentially relevant for the monitoring of antiangiogenic therapy and the development of novel therapeutic combination with immunotherapy","volume":"30","author":"Tartour","year":"2011","journal-title":"Cancer Metastasis Rev."},{"key":"10.1016\/j.phrs.2020.104957_bib0050","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1038\/nature04186","article-title":"VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche","volume":"438","author":"Kaplan","year":"2005","journal-title":"Nature."},{"key":"10.1016\/j.phrs.2020.104957_bib0055","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1007\/s00432-018-2802-6","article-title":"Effects of VEGFR1(+) hematopoietic progenitor cells on pre-metastatic niche formation and in vivo metastasis of breast cancer cells","volume":"145","author":"Meng","year":"2019","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"10.1016\/j.phrs.2020.104957_bib0060","doi-asserted-by":"crossref","first-page":"3781","DOI":"10.1158\/0008-5472.CAN-10-3684","article-title":"Proangiogenic factor PlGF programs CD11b(+) myelomonocytes in breast cancer during differentiation of their hematopoietic progenitors","volume":"71","author":"Laurent","year":"2011","journal-title":"Cancer Res."},{"key":"10.1016\/j.phrs.2020.104957_bib0065","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1007\/s10549-011-1906-3","article-title":"Incremental increase in VEGFR1+ hematopoietic progenitor cells and VEGFR2+ endothelial progenitor cells predicts relapse and lack of tumor response in breast cancer patients","volume":"132","author":"Jain","year":"2012","journal-title":"Breast Cancer Res. Treat."},{"key":"10.1016\/j.phrs.2020.104957_bib0070","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1038\/nrc2524","article-title":"FLT1 and its ligands VEGFB and PlGF: drug targets for anti-angiogenic therapy?","volume":"8","author":"Fischer","year":"2008","journal-title":"Nat. Rev. Cancer"},{"key":"10.1016\/j.phrs.2020.104957_bib0075","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.3389\/fimmu.2018.01310","article-title":"Myeloid-derived suppressor cells hinder the anti-cancer activity of immune checkpoint inhibitors","volume":"9","author":"Weber","year":"2018","journal-title":"Front. Immunol."},{"key":"10.1016\/j.phrs.2020.104957_bib0080","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41423-019-0306-1","article-title":"Myeloid immunosuppression and immune checkpoints in the tumor microenvironment","volume":"17","author":"Nakamura","year":"2020","journal-title":"Cell. Mol. Immunol."},{"key":"10.1016\/j.phrs.2020.104957_bib0085","doi-asserted-by":"crossref","first-page":"E4041","DOI":"10.1073\/pnas.1720948115","article-title":"Macrophages impede CD8 T cells from reaching tumor cells and limit the efficacy of anti-PD-1 treatment","volume":"115","author":"Peranzoni","year":"2018","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.phrs.2020.104957_bib0090","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1007\/s10456-013-9381-6","article-title":"Anti-inflammatory M2, but not pro-inflammatory M1 macrophages promote angiogenesis in vivo","volume":"17","author":"Jetten","year":"2014","journal-title":"Angiogenesis."},{"key":"10.1016\/j.phrs.2020.104957_bib0095","doi-asserted-by":"crossref","first-page":"161","DOI":"10.3109\/08916934.2015.1027816","article-title":"Temporal phenotypic features distinguish polarized macrophages in vitro","volume":"48","author":"Melton","year":"2015","journal-title":"Autoimmunity."},{"key":"10.1016\/j.phrs.2020.104957_bib0100","doi-asserted-by":"crossref","first-page":"72868","DOI":"10.18632\/oncotarget.12108","article-title":"Antitumor activity of a novel anti-vascular endothelial growth factor receptor-1 monoclonal antibody that does not interfere with ligand binding","volume":"7","author":"Graziani","year":"2016","journal-title":"Oncotarget."},{"key":"10.1016\/j.phrs.2020.104957_bib0105","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1111\/jcmm.14755","article-title":"Role of VEGFR-1 in melanoma acquired resistance to the BRAF inhibitor vemurafenib","volume":"24","author":"Atzori","year":"2020","journal-title":"J. Cell. Mol. Med."},{"key":"10.1016\/j.phrs.2020.104957_bib0110","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1111\/j.1365-2133.2010.10200.x","article-title":"Expression of the soluble vascular endothelial growth factor receptor-1 in cutaneous melanoma: role in tumour progression","volume":"164","author":"Ruffini","year":"2011","journal-title":"Br. J. Dermatol."},{"key":"10.1016\/j.phrs.2020.104957_bib0115","doi-asserted-by":"crossref","first-page":"3718","DOI":"10.1172\/JCI61931","article-title":"Suppressing T cell motility induced by anti-CTLA-4 monotherapy improves antitumor effects","volume":"122","author":"Ruocco","year":"2012","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.phrs.2020.104957_bib0120","doi-asserted-by":"crossref","first-page":"3652","DOI":"10.1158\/0008-5472.CAN-14-0957","article-title":"Antimetastatic effects of blocking PD-1 and the adenosine A2A receptor","volume":"74","author":"Mittal","year":"2014","journal-title":"Cancer Res."},{"key":"10.1016\/j.phrs.2020.104957_bib0125","doi-asserted-by":"crossref","first-page":"303","DOI":"10.4103\/0976-500X.119726","article-title":"How to calculate sample size in animal studies?","volume":"4","author":"Charan","year":"2013","journal-title":"J. Pharmacol. Pharmacother."},{"key":"10.1016\/j.phrs.2020.104957_bib0130","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1161\/ATVBAHA.107.158022","article-title":"The molecular basis of VEGFR-1 signal transduction pathways in primary human monocytes","volume":"28","author":"Tchaikovski","year":"2008","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"10.1016\/j.phrs.2020.104957_bib0135","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1186\/s13046-017-0577-2","article-title":"The anti-vascular endothelial growth factor receptor-1 monoclonal antibody D16F7 inhibits invasiveness of human glioblastoma and glioblastoma stem cells","volume":"36","author":"Atzori","year":"2017","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"10.1016\/j.phrs.2020.104957_bib0140","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1159\/000430269","article-title":"Placental growth factor promotes cardiac muscle repair via enhanced neovascularization","volume":"36","author":"Zhang","year":"2015","journal-title":"Cell. Physiol. Biochem."},{"key":"10.1016\/j.phrs.2020.104957_bib0145","doi-asserted-by":"crossref","DOI":"10.1155\/2018\/5690258","article-title":"Expression of PD-1 on CD4+ tumor-infiltrating lymphocytes in tumor microenvironment associated with pathological characteristics of breast Cancer","volume":"2018","author":"Zhao","year":"2018","journal-title":"J. Immunol. Res."},{"key":"10.1016\/j.phrs.2020.104957_bib0150","doi-asserted-by":"crossref","DOI":"10.1016\/j.phrs.2020.104659","article-title":"Role of heterogeneous regulatory T cells in the tumor microenvironment","volume":"153","author":"Wei","year":"2020","journal-title":"Pharmacol. Res."},{"key":"10.1016\/j.phrs.2020.104957_bib0155","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.ccr.2010.11.009","article-title":"HRG inhibits tumor growth and metastasis by inducing macrophage polarization and vessel normalization through downregulation of PlGF","volume":"19","author":"Rolny","year":"2011","journal-title":"Cancer Cell"},{"key":"10.1016\/j.phrs.2020.104957_bib0160","doi-asserted-by":"crossref","first-page":"10071","DOI":"10.1038\/srep10071","article-title":"Larynx carcinoma regulates tumor-associated macrophages through PLGF signaling","volume":"5","author":"Zhou","year":"2015","journal-title":"Sci. Rep."},{"key":"10.1016\/j.phrs.2020.104957_bib0165","first-page":"2749","article-title":"Placental growth factor is a survival factor for tumor endothelial cells and macrophages","volume":"62","author":"Adini","year":"2002","journal-title":"Cancer Res."},{"key":"10.1016\/j.phrs.2020.104957_bib0170","doi-asserted-by":"crossref","first-page":"E1306","DOI":"10.3390\/ijms19051306","article-title":"Positive and negative regulation of angiogenesis by soluble vascular endothelial growth factor Receptor-1","volume":"19","author":"Failla","year":"2018","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.phrs.2020.104957_bib0175","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1124\/jpet.117.244434","article-title":"The anti-vascular endothelial growth factor receptor-1 monoclonal antibody D16F7 inhibits glioma growth and angiogenesis in vivo","volume":"364","author":"Atzori","year":"2018","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"10.1016\/j.phrs.2020.104957_bib0180","doi-asserted-by":"crossref","first-page":"1635","DOI":"10.1158\/0008-5472.CAN-14-3016","article-title":"IL10 and PD-1 cooperate to limit the activity of tumor-specific CD8+ t cells","volume":"75","author":"Sun","year":"2015","journal-title":"Cancer Res."},{"key":"10.1016\/j.phrs.2020.104957_bib0185","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."},{"key":"10.1016\/j.phrs.2020.104957_bib0190","doi-asserted-by":"crossref","DOI":"10.1016\/j.phrs.2019.104609","article-title":"Properties of FDA-approved small molecule protein kinase inhibitors: a 2020 update","volume":"152","author":"Roskoski","year":"2020","journal-title":"Pharmacol. Res."},{"key":"10.1016\/j.phrs.2020.104957_bib0195","first-page":"2514","article-title":"Combined VEGFR and CTLA-4 blockade increases the antigen-presenting function of intratumoral DCs and reduces the suppressive capacity of intratumoral MDSCs","volume":"6","author":"Du Four","year":"2016","journal-title":"Am. J. Cancer Res."},{"key":"10.1016\/j.phrs.2020.104957_bib0200","doi-asserted-by":"crossref","DOI":"10.1080\/2162402X.2016.1232222","article-title":"Regulation of myeloid cells by activated T cells determines the efficacy of PD-1 blockade","volume":"5","author":"Eissler","year":"2016","journal-title":"Oncoimmunology."},{"key":"10.1016\/j.phrs.2020.104957_bib0205","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.aal3604","article-title":"In vivo imaging reveals a tumor-associated macrophage-mediated resistance pathway in anti-PD-1 therapy","volume":"9","author":"Arlauckas","year":"2017","journal-title":"Sci. Transl. Med."}],"container-title":["Pharmacological Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1043661820312652?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1043661820312652?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T10:33:28Z","timestamp":1778582008000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1043661820312652"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9]]},"references-count":41,"alternative-id":["S1043661820312652"],"URL":"https:\/\/doi.org\/10.1016\/j.phrs.2020.104957","relation":{},"ISSN":["1043-6618"],"issn-type":[{"value":"1043-6618","type":"print"}],"subject":[],"published":{"date-parts":[[2020,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Targeting the vascular endothelial growth factor receptor-1 by the monoclonal antibody D16F7 to increase the activity of immune checkpoint inhibitors against cutaneous melanoma","name":"articletitle","label":"Article Title"},{"value":"Pharmacological Research","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.phrs.2020.104957","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 Elsevier Ltd. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"104957"}}