{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T03:41:48Z","timestamp":1789616508104,"version":"build-2803163510"},"reference-count":58,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2021,6,11]],"date-time":"2021-06-11T00:00:00Z","timestamp":1623369600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,6,11]],"date-time":"2021-06-11T00:00:00Z","timestamp":1623369600000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,6,11]],"date-time":"2021-06-11T00:00:00Z","timestamp":1623369600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81772974"],"award-info":[{"award-number":["81772974"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81972882"],"award-info":[{"award-number":["81972882"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002855","name":"Chinese Ministry of Science and Technology","doi-asserted-by":"publisher","award":["2018YFE0114300"],"award-info":[{"award-number":["2018YFE0114300"]}],"id":[{"id":"10.13039\/501100002855","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"crossref","award":["63211137"],"award-info":[{"award-number":["63211137"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Transcoelomic spread of cancer cells across the peritoneal cavity occurs in most initially diagnosed ovarian cancer (OC) patients and accounts for most cancer-related death. However, how OC cells interact with peritoneal stromal cells to evade the immune surveillance remains largely unexplored. Here, through an in vivo genome-wide CRISPR\/Cas9 screen, we identified IL20RA, which decreased dramatically in OC patients during peritoneal metastasis, as a key factor preventing the transcoelomic metastasis of OC. Reconstitution of IL20RA in highly metastatic OC cells greatly suppresses the transcoelomic metastasis. OC cells, when disseminate into the peritoneal cavity, greatly induce peritoneum mesothelial cells to express IL-20 and IL-24, which in turn activate the IL20RA downstream signaling in OC cells to produce mature IL-18, eventually resulting in the polarization of macrophages into the M1-like subtype to clear the cancer cells. Thus, we show an IL-20\/IL20RA-mediated crosstalk between OC and mesothelial cells that supports a metastasis-repressing immune microenvironment.<\/jats:p>","DOI":"10.7554\/elife.66222","type":"journal-article","created":{"date-parts":[[2021,6,11]],"date-time":"2021-06-11T09:00:36Z","timestamp":1623402036000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.66222","source":"Crossref","is-referenced-by-count":25,"title":["A systematic CRISPR screen reveals an IL-20\/IL20RA-mediated immune crosstalk to prevent the ovarian cancer metastasis"],"prefix":"10.7554","volume":"10","author":[{"given":"Jia","family":"Li","sequence":"first","affiliation":[{"name":"The School of Medicine, Nankai University, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Qin","sequence":"additional","affiliation":[{"name":"The School of Medicine, Nankai University, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Shi","sequence":"additional","affiliation":[{"name":"The School of Medicine, Nankai University, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoshuang","family":"Wang","sequence":"additional","affiliation":[{"name":"The School of Medicine, Nankai University, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengyao","family":"Xu","sequence":"additional","affiliation":[{"name":"The School of Medicine, Nankai University, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaosu","family":"Chen","sequence":"additional","affiliation":[{"name":"The School of Medicine, Nankai University, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujia","family":"Zhao","sequence":"additional","affiliation":[{"name":"The School of Medicine, Nankai University, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahao","family":"Han","sequence":"additional","affiliation":[{"name":"The School of Medicine, Nankai University, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongjun","family":"Piao","sequence":"additional","affiliation":[{"name":"The School of Medicine, Nankai University, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenwen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Research Institute of Obstetrics and Gynecology, Tianjin Central Hospital of Obstetrics and Gynecology, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengpeng","family":"Qu","sequence":"additional","affiliation":[{"name":"Department of Gynecological Oncology, Tianjin Central Hospital of Obstetrics and Gynecology, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longlong","family":"Wang","sequence":"additional","affiliation":[{"name":"The School of Medicine, Nankai University, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Xiang","sequence":"additional","affiliation":[{"name":"The School of Medicine, Nankai University, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2530-410X","authenticated-orcid":true,"given":"Yi","family":"Shi","sequence":"additional","affiliation":[{"name":"The School of Medicine, Nankai University, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2021,6,11]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers11101608","article-title":"Productive Cross-Talk with the microenvironment: a critical step in ovarian Cancer metastasis","volume":"11","author":"Agarwal","year":"2019","journal-title":"Cancers"},{"key":"bib2","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2013.00256","article-title":"Getting to know ovarian cancer ascites: opportunities for targeted therapy-based translational research","volume":"3","author":"Ahmed","year":"2013","journal-title":"Frontiers in Oncology"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.cytogfr.2016.02.008","article-title":"RNase L and the NLRP3-inflammasome: An old merchant in a new trade","volume":"29","author":"Banerjee","year":"2016","journal-title":"Cytokine & Growth Factor Reviews"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1016\/j.chom.2015.02.010","article-title":"RNase L activates the NLRP3 inflammasome during viral infections","volume":"17","author":"Chakrabarti","year":"2015","journal-title":"Cell Host & Microbe"},{"key":"bib5","doi-asserted-by":"publisher","first-page":"1509","DOI":"10.1093\/infdis\/jiv221","article-title":"Ifit1 Protects Against Lipopolysaccharide and D-galactosamine-Induced Fatal Hepatitis by Inhibiting Activation of the JNK Pathway","volume":"212","author":"Chang","year":"2015","journal-title":"The Journal of Infectious Diseases"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"4079","DOI":"10.1093\/ndt\/gfr217","article-title":"Human peritoneal mesothelial cells respond to bacterial ligands through a specific subset of Toll-like receptors","volume":"26","author":"Colmont","year":"2011","journal-title":"Nephrology Dialysis Transplantation"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"1441","DOI":"10.1172\/JCI1555","article-title":"Interleukin-12 and interleukin-18 synergistically induce murine tumor regression which involves inhibition of angiogenesis","volume":"101","author":"Coughlin","year":"1998","journal-title":"Journal of Clinical Investigation"},{"key":"bib8","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.47327","article-title":"FAK activity sustains intrinsic and acquired ovarian Cancer resistance to platinum chemotherapy","volume":"8","author":"Diaz Osterman","year":"2019","journal-title":"eLife"},{"key":"bib9","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1189\/jlb.5RU0714-360RR","article-title":"Context-dependent role of IL-18 in cancer biology and counter-regulation by IL-18BP","volume":"97","author":"Fabbi","year":"2015","journal-title":"Journal of Leukocyte Biology"},{"key":"bib10","doi-asserted-by":"publisher","first-page":"538","DOI":"10.1038\/cr.2008.52","article-title":"Genomic analysis of epithelial ovarian cancer","volume":"18","author":"Farley","year":"2008","journal-title":"Cell Research"},{"key":"bib11","doi-asserted-by":"publisher","first-page":"8591","DOI":"10.1158\/0008-5472.CAN-05-0239","article-title":"Caspase-1alpha is down-regulated in human ovarian cancer cells and the overexpression of caspase-1alpha induces apoptosis","volume":"65","author":"Feng","year":"2005","journal-title":"Cancer Research"},{"key":"bib12","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1016\/j.taap.2006.11.021","article-title":"Melanoma differentiation associated gene-7\/interleukin-24 (mda-7\/IL-24): novel gene therapeutic for metastatic melanoma","volume":"224","author":"Fisher","year":"2007","journal-title":"Toxicology and Applied Pharmacology"},{"key":"bib13","doi-asserted-by":"publisher","DOI":"10.1186\/1476-4598-6-11","article-title":"MDA-7\/IL-24 suppresses human ovarian carcinoma growth in vitro and in vivo","volume":"6","author":"Gopalan","year":"2007","journal-title":"Molecular Cancer"},{"key":"bib14","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1530\/ERC-11-0329","article-title":"Implementing an online tool for genome-wide validation of survival-associated biomarkers in ovarian-cancer using microarray data from 1287 patients","volume":"19","author":"Gyorffy","year":"2012","journal-title":"Endocrine-Related Cancer"},{"key":"bib15","doi-asserted-by":"publisher","first-page":"1981","DOI":"10.4049\/jimmunol.1102843","article-title":"Anti-IL-20 monoclonal antibody suppresses breast Cancer progression and bone osteolysis in murine models","volume":"188","author":"Hsu","year":"2012","journal-title":"The Journal of Immunology"},{"key":"bib16","doi-asserted-by":"publisher","DOI":"10.1002\/advs.201900782","article-title":"Genome-Wide CRISPR-Cas9 Screening Identifies NF-\u03baB\/E2F6 Responsible for EGFRvIII-Associated Temozolomide Resistance in Glioblastoma","volume":"6","author":"Huang","year":"2019","journal-title":"Advanced Science"},{"key":"bib17","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2018.00738","article-title":"The Peritoneum: Beyond the Tissue - A Review","volume":"9","author":"Isaza-Restrepo","year":"2018","journal-title":"Frontiers in Physiology"},{"key":"bib18","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1158\/2159-8274.CD-11-0010","article-title":"Ovarian cancer spheroids use myosin-generated force to clear the mesothelium","volume":"1","author":"Iwanicki","year":"2011","journal-title":"Cancer Discovery"},{"key":"bib19","doi-asserted-by":"publisher","first-page":"828","DOI":"10.1038\/nprot.2017.016","article-title":"Genome-scale CRISPR-Cas9 knockout and transcriptional activation screening","volume":"12","author":"Joung","year":"2017","journal-title":"Nature Protocols"},{"key":"bib20","first-page":"1289","article-title":"Endotoxin-induced chemokine expression in murine peritoneal mesothelial cells: the role of toll-like receptor 4","volume":"15","author":"Kato","year":"2004","journal-title":"Journal of the American Society of Nephrology : JASN"},{"key":"bib21","doi-asserted-by":"publisher","first-page":"1463","DOI":"10.1002\/ijc.22874","article-title":"Use of a novel 3D culture model to elucidate the role of mesothelial cells, fibroblasts and extra-cellular matrices on adhesion and invasion of ovarian cancer cells to the omentum","volume":"121","author":"Kenny","year":"2007","journal-title":"International Journal of Cancer"},{"key":"bib22","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1158\/2159-8290.CD-11-0117","article-title":"The first line of intra-abdominal metastatic attack: breaching the mesothelial cell layer","volume":"1","author":"Kenny","year":"2011","journal-title":"Cancer Discovery"},{"key":"bib23","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1038\/nrc3432","article-title":"Meeting the challenge of ascites in ovarian cancer: new avenues for therapy and research","volume":"13","author":"Kipps","year":"2013","journal-title":"Nature Reviews. Cancer"},{"key":"bib24","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0170639","article-title":"IL-22R Ligands IL-20, IL-22, and IL-24 Promote Wound Healing in Diabetic db\/db Mice","volume":"12","author":"Kolumam","year":"2017","journal-title":"PLOS ONE"},{"key":"bib25","doi-asserted-by":"publisher","first-page":"5539","DOI":"10.1074\/jbc.M112.410233","article-title":"Interleukin-20 promotes migration of bladder cancer cells through extracellular signal-regulated kinase (ERK)-mediated MMP-9 protein expression leading to nuclear factor (NF-\u03baB) activation by inducing the up-regulation of p21(WAF1) protein expression","volume":"288","author":"Lee","year":"2013","journal-title":"The Journal of Biological Chemistry"},{"key":"bib26","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1007\/s00018-017-2663-1","article-title":"The peritoneal \"soil\" for a cancerous \"seed\": a comprehensive review of the pathogenesis of intraperitoneal cancer metastases","volume":"75","author":"Miku\u0142a-Pietrasik","year":"2018","journal-title":"Cellular and Molecular Life Sciences : CMLS"},{"key":"bib27","doi-asserted-by":"publisher","first-page":"2885","DOI":"10.1038\/s41388-018-0637-x","article-title":"An evolving story of the metastatic voyage of ovarian cancer cells: cellular and molecular orchestration of the adipose-rich metastatic microenvironment","volume":"38","author":"Motohara","year":"2019","journal-title":"Oncogene"},{"key":"bib28","doi-asserted-by":"publisher","first-page":"1003","DOI":"10.1053\/j.gastro.2009.11.049","article-title":"Stat3 is a negative regulator of intestinal tumor progression in Apc(Min) mice","volume":"138","author":"Musteanu","year":"2010","journal-title":"Gastroenterology"},{"key":"bib29","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1073\/pnas.1821893117","article-title":"CRISPR-mediated modeling and functional validation of candidate tumor suppressor genes in small cell lung cancer","volume":"117","author":"Ng","year":"2020","journal-title":"PNAS"},{"key":"bib30","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1016\/0014-4827(85)90197-1","article-title":"Interactions of human ovarian tumor cells with human mesothelial cells grown on extracellular matrix. An in vitro model system for studying tumor cell adhesion and invasion","volume":"160","author":"Niedbala","year":"1985","journal-title":"Experimental Cell Research"},{"key":"bib31","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1111\/j.1349-7006.2007.00636.x","article-title":"Enhanced suppression of pulmonary metastasis of malignant melanoma cells by combined administration of alpha-galactosylceramide and interleukin-18","volume":"99","author":"Nishio","year":"2008","journal-title":"Cancer Science"},{"key":"bib32","doi-asserted-by":"publisher","first-page":"1116","DOI":"10.1002\/ijc.25757","article-title":"Interleukin (IL)-18, a biomarker of human ovarian carcinoma, is predominantly released as biologically inactive precursor","volume":"129","author":"Orengo","year":"2011","journal-title":"International Journal of Cancer"},{"key":"bib33","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.canlet.2019.07.002","article-title":"Improved anti-tumor efficacy of paclitaxel in combination with MicroRNA-125b-based tumor-associated macrophage repolarization in epithelial ovarian cancer","volume":"461","author":"Parayath","year":"2019","journal-title":"Cancer Letters"},{"key":"bib34","doi-asserted-by":"publisher","first-page":"514","DOI":"10.4049\/jimmunol.179.1.514","article-title":"Nod1\/RICK and TLR signaling regulate chemokine and antimicrobial innate immune responses in mesothelial cells","volume":"179","author":"Park","year":"2007","journal-title":"Journal of Immunology"},{"key":"bib35","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1146\/annurev.immunol.22.012703.104622","article-title":"Interleukin-10 and related cytokines and receptors","volume":"22","author":"Pestka","year":"2004","journal-title":"Annual Review of Immunology"},{"key":"bib36","doi-asserted-by":"publisher","first-page":"1951","DOI":"10.1158\/1535-7163.MCT-17-1002","article-title":"Recombinant MDA-7\/IL24 Suppresses Prostate Cancer Bone Metastasis through Downregulation of the Akt\/Mcl-1 Pathway","volume":"17","author":"Pradhan","year":"2018","journal-title":"Molecular Cancer Therapeutics"},{"key":"bib37","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1002\/ijc.28335","article-title":"Mixed-polarization phenotype of ascites-associated macrophages in human ovarian carcinoma: correlation of CD163 expression, cytokine levels and early relapse","volume":"134","author":"Reinartz","year":"2014","journal-title":"International Journal of Cancer"},{"key":"bib38","doi-asserted-by":"publisher","first-page":"4265","DOI":"10.1158\/1078-0432.CCR-06-0121","article-title":"Clinical and biological effects of recombinant human interleukin-18 administered by intravenous infusion to patients with advanced cancer","volume":"12","author":"Robertson","year":"2006","journal-title":"Clinical Cancer Research"},{"key":"bib39","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1097\/CJI.0b013e31829d7e2e","article-title":"A dose-escalation study of recombinant human interleukin-18 in combination with rituximab in patients with non-Hodgkin lymphoma","volume":"36","author":"Robertson","year":"2013","journal-title":"Journal of Immunotherapy"},{"key":"bib40","doi-asserted-by":"publisher","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":"bib41","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1038\/nri3766","article-title":"The IL-20 subfamily of cytokines--from host defence to tissue homeostasis","volume":"14","author":"Rutz","year":"2014","journal-title":"Nature Reviews. Immunology"},{"key":"bib42","doi-asserted-by":"publisher","first-page":"1625","DOI":"10.1084\/jem.20100199","article-title":"MyD88-mediated signaling prevents development of adenocarcinomas of the Colon: role of interleukin 18","volume":"207","author":"Salcedo","year":"2010","journal-title":"Journal of Experimental Medicine"},{"key":"bib43","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1002\/path.4281","article-title":"Carcinoma-associated fibroblasts derive from mesothelial cells via mesothelial-to-mesenchymal transition in peritoneal metastasis","volume":"231","author":"Sandoval","year":"2013","journal-title":"The Journal of Pathology"},{"key":"bib44","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1126\/science.1247005","article-title":"Genome-scale CRISPR-Cas9 knockout screening in human cells","volume":"343","author":"Shalem","year":"2014","journal-title":"Science"},{"key":"bib45","doi-asserted-by":"publisher","first-page":"7","DOI":"10.3322\/caac.21590","article-title":"Cancer statistics, 2020","volume":"70","author":"Siegel","year":"2020","journal-title":"CA: A\u00a0Cancer Journal for Clinicians"},{"key":"bib46","doi-asserted-by":"publisher","first-page":"925","DOI":"10.1016\/S1470-2045(06)70939-1","article-title":"Mechanisms of transcoelomic metastasis in ovarian cancer","volume":"7","author":"Tan","year":"2006","journal-title":"The Lancet. Oncology"},{"key":"bib47","doi-asserted-by":"publisher","first-page":"859","DOI":"10.1002\/cncr.24100","article-title":"A phase 2, randomized study of SB-485232, rhIL-18, in patients with previously untreated metastatic melanoma","volume":"115","author":"Tarhini","year":"2009","journal-title":"Cancer"},{"key":"bib48","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1007\/s10555-013-9456-2","article-title":"Ovarian cancer microenvironment: implications for cancer dissemination and chemoresistance acquisition","volume":"33","author":"Thibault","year":"2014","journal-title":"Cancer Metastasis Reviews"},{"key":"bib49","doi-asserted-by":"publisher","first-page":"284","DOI":"10.3322\/caac.21456","article-title":"Ovarian cancer statistics, 2018","volume":"68","author":"Torre","year":"2018","journal-title":"CA: A Cancer Journal for Clinicians"},{"key":"bib50","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1038\/nrc3144","article-title":"Rethinking ovarian cancer: recommendations for improving outcomes","volume":"11","author":"Vaughan","year":"2011","journal-title":"Nature Reviews. Cancer"},{"key":"bib51","doi-asserted-by":"publisher","first-page":"873","DOI":"10.1002\/ijc.10268","article-title":"Expression of interleukin-18 in human ovarian carcinoma and normal ovarian epithelium: evidence for defective processing in tumor cells","volume":"98","author":"Wang","year":"2002","journal-title":"International Journal of Cancer"},{"key":"bib52","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1007\/s10585-012-9562-5","article-title":"Inhibition of focal adhesion kinase (FAK) activity prevents anchorage-independent ovarian carcinoma cell growth and tumor progression","volume":"30","author":"Ward","year":"2013","journal-title":"Clinical & Experimental Metastasis"},{"key":"bib53","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1016\/j.cytogfr.2012.08.004","article-title":"Interleukin 24: mechanisms and therapeutic potential of an anti-cancer gene","volume":"23","author":"Whitaker","year":"2012","journal-title":"Cytokine & Growth Factor Reviews"},{"key":"bib54","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2017.00024","article-title":"The Unique Molecular and Cellular Microenvironment of Ovarian Cancer","volume":"7","author":"Worzfeld","year":"2017","journal-title":"Frontiers in Oncology"},{"key":"bib55","doi-asserted-by":"publisher","first-page":"997","DOI":"10.1111\/j.1445-1433.2004.03220.x","article-title":"Peritoneal mesothelial cells produce inflammatory related cytokines","volume":"74","author":"Yao","year":"2004","journal-title":"ANZ Journal of Surgery"},{"key":"bib56","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0063588","article-title":"IL-26 promotes the proliferation and survival of human gastric cancer cells by regulating the balance of STAT1 and STAT3 activation","volume":"8","author":"You","year":"2013","journal-title":"PLOS ONE"},{"key":"bib57","doi-asserted-by":"publisher","first-page":"4912","DOI":"10.4049\/jimmunol.1002046","article-title":"IL-18 production downstream of the Nlrp3 inflammasome confers protection against colorectal tumor formation","volume":"185","author":"Zaki","year":"2010","journal-title":"The Journal of Immunology"},{"key":"bib58","doi-asserted-by":"publisher","DOI":"10.1186\/1757-2215-7-19","article-title":"A high M1\/M2 ratio of tumor-associated macrophages is associated with extended survival in ovarian cancer patients","volume":"7","author":"Zhang","year":"2014","journal-title":"Journal of Ovarian Research"}],"container-title":["eLife"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdn.elifesciences.org\/articles\/66222\/elife-66222-v1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdn.elifesciences.org\/articles\/66222\/elife-66222-v1.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/elifesciences.org\/articles\/66222","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T21:10:49Z","timestamp":1697058649000},"score":1,"resource":{"primary":{"URL":"https:\/\/elifesciences.org\/articles\/66222"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,11]]},"references-count":58,"alternative-id":["10.7554\/eLife.66222"],"URL":"https:\/\/doi.org\/10.7554\/elife.66222","archive":["CLOCKSS"],"relation":{"has-review":[{"id-type":"doi","id":"10.7554\/eLife.66222.sa1","asserted-by":"object"},{"id-type":"doi","id":"10.7554\/eLife.66222.sa2","asserted-by":"object"}],"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.01.03.425154","asserted-by":"object"}]},"ISSN":["2050-084X"],"issn-type":[{"value":"2050-084X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,11]]},"assertion":[{"value":"single anonymised","name":"peer_review_transparency","label":"Peer review transparency","group":{"name":"peer_review_taxonomy"}},{"value":"other reviewer(s), editor","name":"peer_review_interaction","label":"Peer review interaction","group":{"name":"peer_review_taxonomy"}},{"value":"review summaries, review reports, author\/editor communication, reviewer identities reviewer opt in, editor identities","name":"peer_review_published","label":"Peer review published","group":{"name":"peer_review_taxonomy"}},{"value":"open (sign in with ORCID iD required)","name":"post_publication_commenting","label":"Post publication commenting","group":{"name":"post_publication_commenting"}}],"article-number":"e66222"}}