{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T22:38:34Z","timestamp":1790807914628,"version":"4.1.0"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2018,5,1]],"date-time":"2018-05-01T00:00:00Z","timestamp":1525132800000},"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":[[2018,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>C5aR1 (CD88), a receptor for complement anaphylatoxin C5a, is a potent immune mediator. Its impact on malignant growth and dissemination of non\u2013small cell lung cancer cells is poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To investigate the contribution of the C5a\/C5aR1 axis to the malignant phenotype of non\u2013small cell lung cancer cells, particularly in skeletal colonization, a preferential lung metastasis site.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Association between C5aR1 expression and clinical outcome was assessed in silico and validated by immunohistochemistry. Functional significance was evaluated by lentiviral gene silencing and ligand l-aptamer inhibition in in vivo models of lung cancer bone metastasis. In vitro functional assays for signaling, migration, invasion, metalloprotease activity, and osteoclastogenesis were also performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>High levels of C5aR1 in human lung tumors were significantly associated with shorter recurrence-free survival, overall survival, and bone metastasis. Silencing of C5aR1 in lung cancer cells led to a substantial reduction in skeletal metastatic burden and osteolysis in in vivo models. Furthermore, metalloproteolytic, migratory, and invasive tumor cell activities were modulated in vitro by C5aR1 stimulation or gene silencing. l-Aptamer blockade or C5aR1 silencing significantly reduced the osseous metastatic activity of lung cancer cells in vivo. This effect was associated with decreased osteoclastogenic activity in vitro and was rescued by the exogenous addition of the chemokine CXCL16.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Disruption of C5aR1 signaling in lung cancer cells abrogates their tumor-associated osteoclastogenic activity, impairing osseous colonization. This study unveils the role played by the C5a\/C5aR1 axis in lung cancer dissemination and supports its potential use as a novel therapeutic target.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.201703-0660oc","type":"journal-article","created":{"date-parts":[[2018,1,12]],"date-time":"2018-01-12T11:20:03Z","timestamp":1515756003000},"page":"1164-1176","source":"Crossref","is-referenced-by-count":98,"title":["Blockade of the Complement C5a\/C5aR1 Axis Impairs Lung Cancer Bone Metastasis by CXCL16-mediated Effects"],"prefix":"10.1093","volume":"197","author":[{"given":"Daniel","family":"Ajona","sequence":"first","affiliation":[{"name":"Center for Applied Medical Research, Program in Solid Tumors and Biomarkers, Pamplona, Spain"},{"name":"IdiSNA (Navarra Institute for Health Research), Pamplona, Spain"},{"name":"CIBERONC (Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer), Spain"},{"name":"Department of Biochemistry and Genetics, School of Sciences, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Zandueta","sequence":"additional","affiliation":[{"name":"Center for Applied Medical Research, Program in Solid Tumors and Biomarkers, Pamplona, Spain"},{"name":"IdiSNA (Navarra Institute for Health Research), Pamplona, Spain"},{"name":"CIBERONC (Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer), Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leticia","family":"Corrales","sequence":"additional","affiliation":[{"name":"Center for Applied Medical Research, Program in Solid Tumors and Biomarkers, Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haritz","family":"Moreno","sequence":"additional","affiliation":[{"name":"Center for Applied Medical Research, Program in Solid Tumors and Biomarkers, Pamplona, Spain"},{"name":"IdiSNA (Navarra Institute for Health Research), Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda J.","family":"Pajares","sequence":"additional","affiliation":[{"name":"Center for Applied Medical Research, Program in Solid Tumors and Biomarkers, Pamplona, Spain"},{"name":"IdiSNA (Navarra Institute for Health Research), Pamplona, Spain"},{"name":"CIBERONC (Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer), Spain"},{"name":"Department of Histology and Pathology, School of Medicine, University of Navarra, Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Ortiz-Espinosa","sequence":"additional","affiliation":[{"name":"Center for Applied Medical Research, Program in Solid Tumors and Biomarkers, Pamplona, Spain"},{"name":"CIBERONC (Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer), Spain"},{"name":"Department of Biochemistry and Genetics, School of Sciences, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Mart\u00ednez-Terroba","sequence":"additional","affiliation":[{"name":"Center for Applied Medical Research, Program in Solid Tumors and Biomarkers, Pamplona, Spain"},{"name":"Department of Histology and Pathology, School of Medicine, University of Navarra, Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naiara","family":"Perurena","sequence":"additional","affiliation":[{"name":"Center for Applied Medical Research, Program in Solid Tumors and Biomarkers, Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando J.","family":"de Miguel","sequence":"additional","affiliation":[{"name":"Center for Applied Medical Research, Program in Solid Tumors and Biomarkers, Pamplona, Spain"},{"name":"Department of Biochemistry and Genetics, School of Sciences, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eloisa","family":"Jantus-Lewintre","sequence":"additional","affiliation":[{"name":"CIBERONC (Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer), Spain"},{"name":"Molecular Oncology Laboratory, Fundaci\u00f3n Investigaci\u00f3n, Hospital General Universitario de Valencia, Valencia, Spain"},{"name":"Department of Biotechnology, Universitat Polit\u00e8cnica de Val\u00e8ncia, Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Camps","sequence":"additional","affiliation":[{"name":"CIBERONC (Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer), Spain"},{"name":"Molecular Oncology Laboratory, Fundaci\u00f3n Investigaci\u00f3n, Hospital General Universitario de Valencia, Valencia, Spain"},{"name":"Department of Medical Oncology, Hospital General Universitario de Valencia, Valencia, Spain; and"},{"name":"Department of Medicine, Universitat de Val\u00e8ncia, Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvestre","family":"Vicent","sequence":"additional","affiliation":[{"name":"Center for Applied Medical Research, Program in Solid Tumors and Biomarkers, Pamplona, Spain"},{"name":"IdiSNA (Navarra Institute for Health Research), Pamplona, Spain"},{"name":"CIBERONC (Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer), Spain"},{"name":"Department of Histology and Pathology, School of Medicine, University of Navarra, Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jackeline","family":"Agorreta","sequence":"additional","affiliation":[{"name":"Center for Applied Medical Research, Program in Solid Tumors and Biomarkers, Pamplona, Spain"},{"name":"IdiSNA (Navarra Institute for Health Research), Pamplona, Spain"},{"name":"CIBERONC (Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer), Spain"},{"name":"Department of Histology and Pathology, School of Medicine, University of Navarra, Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis M.","family":"Montuenga","sequence":"additional","affiliation":[{"name":"Center for Applied Medical Research, Program in Solid Tumors and Biomarkers, Pamplona, Spain"},{"name":"IdiSNA (Navarra Institute for Health Research), Pamplona, Spain"},{"name":"CIBERONC (Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer), Spain"},{"name":"Department of Histology and Pathology, School of Medicine, University of Navarra, Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruben","family":"Pio","sequence":"additional","affiliation":[{"name":"Center for Applied Medical Research, Program in Solid Tumors and Biomarkers, Pamplona, Spain"},{"name":"IdiSNA (Navarra Institute for Health Research), Pamplona, Spain"},{"name":"CIBERONC (Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer), Spain"},{"name":"Department of Biochemistry and Genetics, School of Sciences, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Lecanda","sequence":"additional","affiliation":[{"name":"Center for Applied Medical Research, Program in Solid Tumors and Biomarkers, Pamplona, Spain"},{"name":"IdiSNA (Navarra Institute for Health Research), Pamplona, Spain"},{"name":"CIBERONC (Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer), Spain"},{"name":"Department of Histology and Pathology, School of Medicine, University of Navarra, Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,5,1]]},"reference":[{"key":"2026032023191728200_bib1","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.smim.2013.04.001","article-title":"Complement inhibition in cancer therapy","volume":"25","author":"Pio","year":"2013","journal-title":"Semin Immunol"},{"key":"2026032023191728200_bib2","doi-asserted-by":"crossref","first-page":"2753","DOI":"10.1016\/j.molimm.2009.04.027","article-title":"The role of the anaphylatoxins in health and disease","volume":"46","author":"Klos","year":"2009","journal-title":"Mol Immunol"},{"key":"2026032023191728200_bib3","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1038\/icb.2016.43","article-title":"Discovery of functionally selective C5aR2 ligands: novel modulators of C5a signalling","volume":"94","author":"Croker","year":"2016","journal-title":"Immunol Cell Biol"},{"key":"2026032023191728200_bib4","doi-asserted-by":"crossref","first-page":"4674","DOI":"10.4049\/jimmunol.1201654","article-title":"Anaphylatoxin C5a creates a favorable microenvironment for lung cancer progression","volume":"189","author":"Corrales","year":"2012","journal-title":"J Immunol"},{"key":"2026032023191728200_bib5","doi-asserted-by":"crossref","first-page":"6310","DOI":"10.1158\/0008-5472.CAN-03-2328","article-title":"Expression of complement factor H by lung cancer cells: effects on the activation of the alternative pathway of complement","volume":"64","author":"Ajona","year":"2004","journal-title":"Cancer Res"},{"key":"2026032023191728200_bib6","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1093\/jnci\/djt205","article-title":"Investigation of complement activation product c4d as a diagnostic and prognostic biomarker for lung cancer","volume":"105","author":"Ajona","year":"2013","journal-title":"J Natl Cancer Inst"},{"key":"2026032023191728200_bib7","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.lungcan.2013.04.020","article-title":"Overexpression of CD88 predicts poor prognosis in non-small-cell lung cancer","volume":"81","author":"Gu","year":"2013","journal-title":"Lung Cancer"},{"key":"2026032023191728200_bib8","doi-asserted-by":"crossref","first-page":"5991","DOI":"10.4049\/jimmunol.178.9.5991","article-title":"Down-regulation of human complement factor H sensitizes non-small cell lung cancer cells to complement attack and reduces in vivo tumor growth","volume":"178","author":"Ajona","year":"2007","journal-title":"J Immunol"},{"key":"2026032023191728200_bib9","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.molimm.2007.04.025","article-title":"Non-small cell lung cancer cells produce a functional set of complement factor I and its soluble cofactors","volume":"45","author":"Okroj","year":"2008","journal-title":"Mol Immunol"},{"key":"2026032023191728200_bib10","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1038\/ni.1655","article-title":"Modulation of the antitumor immune response by complement","volume":"9","author":"Markiewski","year":"2008","journal-title":"Nat Immunol"},{"key":"2026032023191728200_bib11","doi-asserted-by":"crossref","first-page":"2985","DOI":"10.4049\/jimmunol.1200846","article-title":"Opposing roles for complement component C5a in tumor progression and the tumor microenvironment","volume":"189","author":"Gunn","year":"2012","journal-title":"J Immunol"},{"key":"2026032023191728200_bib12","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1158\/2159-8290.CD-15-1412","article-title":"Autocrine complement inhibits IL10-dependent T-cell-mediated antitumor immunity to promote tumor progression","volume":"6","author":"Wang","year":"2016","journal-title":"Cancer Discov"},{"key":"2026032023191728200_bib13","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1593\/neo.121262","article-title":"Genetic and pharmacologic inhibition of complement impairs endothelial cell function and ablates ovarian cancer neovascularization","volume":"14","author":"Nunez-Cruz","year":"2012","journal-title":"Neoplasia"},{"key":"2026032023191728200_bib14","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1007\/s12282-015-0654-3","article-title":"Influence of the C5a-C5a receptor system on breast cancer progression and patient prognosis","volume":"23","author":"Imamura","year":"2016","journal-title":"Breast Cancer"},{"key":"2026032023191728200_bib15","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1016\/j.celrep.2014.02.014","article-title":"Autocrine effects of tumor-derived complement","volume":"6","author":"Cho","year":"2014","journal-title":"Cell Reports"},{"key":"2026032023191728200_bib16","doi-asserted-by":"crossref","first-page":"3995","DOI":"10.3892\/ol.2016.5137","article-title":"C5a receptor expression is associated with poor prognosis in urothelial cell carcinoma patients treated with radical cystectomy or nephroureterectomy","volume":"12","author":"Wada","year":"2016","journal-title":"Oncol Lett"},{"key":"2026032023191728200_bib17","doi-asserted-by":"crossref","first-page":"2004","DOI":"10.1158\/1078-0432.CCR-12-1204","article-title":"Enhancement of human cancer cell motility and invasiveness by anaphylatoxin C5a via aberrantly expressed C5a receptor (CD88)","volume":"19","author":"Nitta","year":"2013","journal-title":"Clin Cancer Res"},{"key":"2026032023191728200_bib18","doi-asserted-by":"crossref","first-page":"1844","DOI":"10.3892\/or.2015.3800","article-title":"C5aR is frequently expressed in metastatic renal cell carcinoma and plays a crucial role in cell invasion via the ERK and PI3 kinase pathways","volume":"33","author":"Maeda","year":"2015","journal-title":"Oncol Rep"},{"key":"2026032023191728200_bib19","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.yexmp.2015.10.001","article-title":"C5a receptor enhances hepatocellular carcinoma cell invasiveness via activating ERK1\/2-mediated epithelial-mesenchymal transition","volume":"100","author":"Hu","year":"2016","journal-title":"Exp Mol Pathol"},{"key":"2026032023191728200_bib20","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1038\/nrc3055","article-title":"Cancer to bone: a fatal attraction","volume":"11","author":"Weilbaecher","year":"2011","journal-title":"Nat Rev Cancer"},{"key":"2026032023191728200_bib21","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1164\/rccm.201503-0440SO","article-title":"Bone metastases in lung cancer. Potential novel approaches to therapy","volume":"192","author":"Vicent","year":"2015","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032023191728200_bib22","doi-asserted-by":"crossref","first-page":"3758","DOI":"10.1038\/onc.2010.130","article-title":"Novel alternatively spliced ADAM8 isoforms contribute to the aggressive bone metastatic phenotype of lung cancer","volume":"29","author":"Hern\u00e1ndez","year":"2010","journal-title":"Oncogene"},{"key":"2026032023191728200_bib23","doi-asserted-by":"crossref","first-page":"2275","DOI":"10.1158\/0008-5472.CAN-07-6493","article-title":"A novel lung cancer signature mediates metastatic bone colonization by a dual mechanism","volume":"68","author":"Vicent","year":"2008","journal-title":"Cancer Res"},{"key":"2026032023191728200_bib24","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.molonc.2013.11.001","article-title":"RHOB influences lung adenocarcinoma metastasis and resistance in a host-sensitive manner","volume":"8","author":"Luis-Ravelo","year":"2014","journal-title":"Mol Oncol"},{"key":"2026032023191728200_bib25","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1186\/1476-4598-9-139","article-title":"Complement activation mediates cetuximab inhibition of non-small cell lung cancer tumor growth in vivo","volume":"9","author":"Hsu","year":"2010","journal-title":"Mol Cancer"},{"key":"2026032023191728200_bib26","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1158\/0008-5472.CAN-10-1708","article-title":"PDGFR signaling blockade in marrow stroma impairs lung cancer bone metastasis","volume":"71","author":"Catena","year":"2011","journal-title":"Cancer Res"},{"key":"2026032023191728200_bib27","doi-asserted-by":"crossref","first-page":"5090","DOI":"10.1038\/onc.2013.440","article-title":"A gene signature of bone metastatic colonization sensitizes for tumor-induced osteolysis and predicts survival in lung cancer","volume":"33","author":"Luis-Ravelo","year":"2014","journal-title":"Oncogene"},{"key":"2026032023191728200_bib28","doi-asserted-by":"crossref","first-page":"2594","DOI":"10.1002\/jcb.23186","article-title":"Complement C3a and C5a modulate osteoclast formation and inflammatory response of osteoblasts in synergism with IL-1\u03b2","volume":"112","author":"Ignatius","year":"2011","journal-title":"J Cell Biochem"},{"key":"2026032023191728200_bib29","doi-asserted-by":"crossref","first-page":"4606","DOI":"10.1158\/0008-5472.CAN-13-0305","article-title":"Myeloid-derived suppressor cells as osteoclast progenitors: a novel target for controlling osteolytic bone metastasis","volume":"73","author":"Sawant","year":"2013","journal-title":"Cancer Res"},{"key":"2026032023191728200_bib30","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.4161\/onci.21990","article-title":"Myeloid-derived suppressor cells expand during breast cancer progression and promote tumor-induced bone destruction","volume":"1","author":"Danilin","year":"2012","journal-title":"OncoImmunology"},{"key":"2026032023191728200_bib31","article-title":"Blockade of C5aR impairs bone metastases by decreasing osteoclastic activity","author":"Ajona"},{"key":"2026032023191728200_bib32","volume-title":"Pathology and genetics. Tumours of the lung, pleura, thymus and heart","author":"Travis","year":"2004"},{"key":"2026032023191728200_bib33","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1158\/2159-8290.CD-16-1184","article-title":"A combined PD-1\/C5a blockade synergistically protects against lung cancer growth and metastasis","volume":"7","author":"Ajona","year":"2017","journal-title":"Cancer Discov"},{"key":"2026032023191728200_bib34","doi-asserted-by":"crossref","first-page":"2236","DOI":"10.1038\/mt.2013.178","article-title":"A novel C5a-neutralizing mirror-image (l-)aptamer prevents organ failure and improves survival in experimental sepsis","volume":"21","author":"Hoehlig","year":"2013","journal-title":"Mol Ther"},{"key":"2026032023191728200_bib35","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1164\/rccm.201110-1826OC","article-title":"Receptor of activated protein C promotes metastasis and correlates with clinical outcome in lung adenocarcinoma","volume":"186","author":"Ant\u00f3n","year":"2012","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032023191728200_bib36","doi-asserted-by":"crossref","first-page":"6105","DOI":"10.1038\/sj.onc.1207815","article-title":"Mechanisms underlying differential expression of interleukin-8 in breast cancer cells","volume":"23","author":"Freund","year":"2004","journal-title":"Oncogene"},{"key":"2026032023191728200_bib37","doi-asserted-by":"crossref","first-page":"2171","DOI":"10.18632\/oncotarget.1426","article-title":"Chemokines in tumor progression and metastasis","volume":"4","author":"Sarvaiya","year":"2013","journal-title":"Oncotarget"},{"key":"2026032023191728200_bib38","doi-asserted-by":"crossref","first-page":"e99056","DOI":"10.1371\/journal.pone.0099056","article-title":"CXCL16 and CXCR6 are coexpressed in human lung cancer in vivo and mediate the invasion of lung cancer cell lines in vitro","volume":"9","author":"Hu","year":"2014","journal-title":"PLoS One"},{"key":"2026032023191728200_bib39","doi-asserted-by":"crossref","first-page":"9985","DOI":"10.18632\/oncotarget.3194","article-title":"CXCR6 expression in non-small cell lung carcinoma supports metastatic process via modulating metalloproteinases","volume":"6","author":"Mir","year":"2015","journal-title":"Oncotarget"},{"key":"2026032023191728200_bib40","doi-asserted-by":"crossref","first-page":"1362","DOI":"10.1111\/j.1349-7006.2008.00833.x","article-title":"CXCR6 is expressed in human prostate cancer in vivo and is involved in the in vitro invasion of PC3 and LNCap cells","volume":"99","author":"Hu","year":"2008","journal-title":"Cancer Sci"},{"key":"2026032023191728200_bib41","first-page":"419","article-title":"Clinical significance of CXCL16\/CXCR6 expression in patients with prostate cancer","volume":"4","author":"Ha","year":"2011","journal-title":"Mol Med Rep"},{"key":"2026032023191728200_bib42","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.molimm.2017.05.012","article-title":"Intracellular complement - the complosome - in immune cell regulation","volume":"89","author":"Arbore","year":"2017","journal-title":"Mol Immunol"},{"key":"2026032023191728200_bib43","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.1111\/j.1365-2222.2005.02383.x","article-title":"Expression of CXCR6 and its ligand CXCL16 in the lung in health and disease","volume":"35","author":"Morgan","year":"2005","journal-title":"Clin Exp Allergy"},{"key":"2026032023191728200_bib44","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1007\/s00011-015-0905-y","article-title":"CXCL16 upregulates RANKL expression in rheumatoid arthritis synovial fibroblasts through the JAK2\/STAT3 and p38\/MAPK signaling pathway","volume":"65","author":"Li","year":"2016","journal-title":"Inflamm Res"},{"key":"2026032023191728200_bib45","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.imbio.2012.01.020","article-title":"Does complement play a role in bone development and regeneration?","volume":"218","author":"Schoengraf","year":"2013","journal-title":"Immunobiology"},{"key":"2026032023191728200_bib46","doi-asserted-by":"crossref","first-page":"e27897","DOI":"10.4161\/onci.27897","article-title":"Role of the complement system in NK cell-mediated antitumor T-cell responses","volume":"3","author":"Janelle","year":"2014","journal-title":"OncoImmunology"},{"key":"2026032023191728200_bib47","doi-asserted-by":"crossref","first-page":"3454","DOI":"10.1158\/0008-5472.CAN-14-0157","article-title":"Complement c5a receptor facilitates cancer metastasis by altering T-cell responses in the metastatic niche","volume":"74","author":"Vadrevu","year":"2014","journal-title":"Cancer Res"},{"key":"2026032023191728200_bib48","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1016\/j.cell.2017.02.025","article-title":"Complement component 3 adapts the cerebrospinal fluid for leptomeningeal metastasis","volume":"168","author":"Boire","year":"2017","journal-title":"Cell"},{"key":"2026032023191728200_bib49","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1038\/nrc3239","article-title":"The blockade of immune checkpoints in cancer immunotherapy","volume":"12","author":"Pardoll","year":"2012","journal-title":"Nat Rev Cancer"},{"key":"2026032023191728200_bib50","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1038\/nrc3973","article-title":"Evolving synergistic combinations of targeted immunotherapies to combat cancer","volume":"15","author":"Melero","year":"2015","journal-title":"Nat Rev Cancer"},{"key":"2026032023191728200_bib51","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.cell.2015.03.030","article-title":"Immune checkpoint targeting in cancer therapy: toward combination strategies with curative potential","volume":"161","author":"Sharma","year":"2015","journal-title":"Cell"}],"container-title":["American Journal of Respiratory and Critical Care Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/197\/9\/1164\/67123281\/ajrccm_197_9_1164.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/197\/9\/1164\/67123281\/ajrccm_197_9_1164.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T03:19:33Z","timestamp":1774063173000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajrccm\/article\/197\/9\/1164\/8498727"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,5,1]]},"references-count":51,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2018,5,1]]},"published-print":{"date-parts":[[2018,5,1]]}},"URL":"https:\/\/doi.org\/10.1164\/rccm.201703-0660oc","relation":{},"ISSN":["1073-449X","1535-4970"],"issn-type":[{"value":"1073-449X","type":"print"},{"value":"1535-4970","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2018,5]]},"published":{"date-parts":[[2018,5,1]]}}}