{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T17:36:29Z","timestamp":1774373789051,"version":"3.50.1"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2020,11,19]],"date-time":"2020-11-19T00:00:00Z","timestamp":1605744000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81573462"],"award-info":[{"award-number":["81573462"]}],"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":["81903658"],"award-info":[{"award-number":["81903658"]}],"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":["81703560"],"award-info":[{"award-number":["81703560"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018617","name":"Liaoning Revitalization Talents Program","doi-asserted-by":"crossref","award":["XLYC1807201"],"award-info":[{"award-number":["XLYC1807201"]}],"id":[{"id":"10.13039\/501100018617","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Major Special S&T Projects in Liaoning Province","award":["2019JH1\/10300005"],"award-info":[{"award-number":["2019JH1\/10300005"]}]},{"name":"Liaoning Province Scientific Research Foundation","award":["ZF2019038"],"award-info":[{"award-number":["ZF2019038"]}]},{"name":"Shenyang Science and Technology Projects","award":["19\u2013109\u20134-09"],"award-info":[{"award-number":["19\u2013109\u20134-09"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,7,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>NLRP3 inflammasome was introduced as a double-edged sword in tumorigenesis and influenced immunotherapy response by modulating host immunity. However, a systematic assessment of the NLRP3-inflammasome-related genes across human cancers is lacking, and the predictive role of NLRP3 inflammasome in cancer immunotherapy (CIT) response remains unexplored. Thus, in this study, we performed a pan-cancer analysis of NLRP3-inflammasome-related genes across 24 human cancers. Out of these 24 cancers, 15 cancers had significantly different expression of NLRP3-inflammasome-related genes between normal and tumor samples. Meanwhile, Cox regression analysis showed that the NLRP3 inflammasome score could be served as an independent prognostic factor in skin cutaneous melanoma. Further analysis indicated that NLRP3 inflammasome may influence tumor immunity mainly by mediating tumor-infiltrating lymphocytes and macrophages, and the effect of NLRP3 inflammasome on immunity is diverse across tumor types in tumor microenvironment. We also found that the NLRP3 inflammasome score could be a stronger predictor for immune signatures compared with tumor mutation burden (TMB) and glycolytic activity, which have been reported as immune predictors. Furthermore, analysis of the association between NLRP3 inflammasome and CIT response using six CIT response datasets revealed the predictive value of NLRP3 inflammasome for immunotherapy response of patients in diverse cancers. Our study illustrates the characterization of NLRP3 inflammasome in multiple cancer types and highlights its potential value as a predictive biomarker of CIT response, which can pave the way for further investigation of the prognostic and therapeutic potentials of NLRP3 inflammasome.<\/jats:p>","DOI":"10.1093\/bib\/bbaa345","type":"journal-article","created":{"date-parts":[[2020,10,31]],"date-time":"2020-10-31T12:10:41Z","timestamp":1604146241000},"source":"Crossref","is-referenced-by-count":155,"title":["Pan-cancer analysis of NLRP3 inflammasome with potential implications in prognosis and immunotherapy in human cancer"],"prefix":"10.1093","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4084-3358","authenticated-orcid":false,"given":"Mingyi","family":"Ju","sequence":"first","affiliation":[{"name":"China Medical University, Liaoning, China"}]},{"given":"Jia","family":"Bi","sequence":"additional","affiliation":[{"name":"China Medical University, Liaoning, China"}]},{"given":"Qian","family":"Wei","sequence":"additional","affiliation":[{"name":"China Medical University, Liaoning, China"}]},{"given":"Longyang","family":"Jiang","sequence":"additional","affiliation":[{"name":"China Medical University, Liaoning, China"}]},{"given":"Qiutong","family":"Guan","sequence":"additional","affiliation":[{"name":"China Medical University, Liaoning, China"}]},{"given":"Ming","family":"Zhang","sequence":"additional","affiliation":[{"name":"China Medical University, Liaoning, China"}]},{"given":"Xinyue","family":"Song","sequence":"additional","affiliation":[{"name":"China Medical University, Liaoning, China"}]},{"given":"Ting","family":"Chen","sequence":"additional","affiliation":[{"name":"China Medical University, Liaoning, China"}]},{"given":"Jingyi","family":"Fan","sequence":"additional","affiliation":[{"name":"China Medical University, Liaoning, China"}]},{"given":"Xiaojuan","family":"Li","sequence":"additional","affiliation":[{"name":"China Medical University, Liaoning, China"}]},{"given":"Minjie","family":"Wei","sequence":"additional","affiliation":[{"name":"China Medical University, Liaoning, China"}]},{"given":"Lin","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang City, 110122, Liaoning, China"}]}],"member":"286","published-online":{"date-parts":[[2020,11,20]]},"reference":[{"key":"2021072117024462900_ref1","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1126\/science.aar4060","article-title":"Cancer immunotherapy using checkpoint blockade","volume":"359","author":"Ribas","year":"2018","journal-title":"Science (New York, NY)"},{"key":"2021072117024462900_ref2","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.immuni.2019.12.011","article-title":"Top 10 challenges in cancer immunotherapy","volume":"52","author":"Hegde","year":"2020","journal-title":"Immunity"},{"key":"2021072117024462900_ref3","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1093\/annonc\/mdy495","article-title":"Development of tumor mutation burden as an immunotherapy biomarker: utility for the oncology clinic","volume":"30","author":"Chan","year":"2019","journal-title":"Annals Oncol: Offic J Eur Soc Med Oncol"},{"key":"2021072117024462900_ref4","doi-asserted-by":"crossref","first-page":"115","DOI":"10.2217\/imt-2016-0138","article-title":"Eosinophilic count as a biomarker for prognosis of melanoma patients and its importance in the response to immunotherapy","volume":"9","author":"Moreira","year":"2017","journal-title":"Immunotherapy"},{"key":"2021072117024462900_ref5","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1158\/1535-7163.MCT-14-0983","article-title":"PD-L1 expression as a predictive biomarker in cancer immunotherapy","volume":"14","author":"Patel","year":"2015","journal-title":"Mol Cancer Ther"},{"key":"2021072117024462900_ref6","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1158\/2326-6066.CIR-16-0013","article-title":"Deep sequencing of T-cell receptor DNA as a biomarker of clonally expanded TILs in breast cancer after immunotherapy","volume":"4","author":"Page","year":"2016","journal-title":"Cancer Immunol Res"},{"key":"2021072117024462900_ref7","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/j.ebiom.2019.03.068","article-title":"Increased glycolysis correlates with elevated immune activity in tumor immune microenvironment","volume":"42","author":"Jiang","year":"2019","journal-title":"EBioMedicine"},{"key":"2021072117024462900_ref8","doi-asserted-by":"crossref","first-page":"4022","DOI":"10.1200\/JCO.2010.28.4257","article-title":"Tumor-host interactions: a far-reaching relationship","volume":"28","author":"McAllister","year":"2010","journal-title":"J Clin Oncol Off J Am Soc Clin Oncol"},{"key":"2021072117024462900_ref9","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1111\/imr.12296","article-title":"Regulation of inflammasome activation","volume":"265","author":"Man","year":"2015","journal-title":"Immunol Rev"},{"key":"2021072117024462900_ref10","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1186\/s12943-018-0900-3","article-title":"Role of the NLRP3 inflammasome in cancer","volume":"17","author":"Moossavi","year":"2018","journal-title":"Mol Cancer"},{"key":"2021072117024462900_ref11","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/s41568-019-0123-y","article-title":"Diverging inflammasome signals in tumorigenesis and potential targeting","volume":"19","author":"Karki","year":"2019","journal-title":"Nat Rev Cancer"},{"key":"2021072117024462900_ref12","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1084\/jem.20100050","article-title":"The NLRP3 inflammasome functions as a negative regulator of tumorigenesis during colitis-associated cancer","volume":"207","author":"Allen","year":"2010","journal-title":"J Exp Med"},{"key":"2021072117024462900_ref13","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1016\/j.immuni.2015.08.013","article-title":"The Nlrp3 Inflammasome suppresses colorectal cancer metastatic growth in the liver by promoting natural killer cell Tumoricidal activity","volume":"43","author":"Dupaul-Chicoine","year":"2015","journal-title":"Immunity"},{"key":"2021072117024462900_ref14","doi-asserted-by":"crossref","first-page":"12994","DOI":"10.1073\/pnas.1705165114","article-title":"Cancer cells induce interleukin-22 production from memory CD4 T cells via interleukin-1 to promote tumor growth","volume":"114","author":"Voigt","year":"2017","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2021072117024462900_ref15","doi-asserted-by":"crossref","first-page":"2570","DOI":"10.1172\/JCI133055","article-title":"A tumor-intrinsic PD-L1\/NLRP3 inflammasome signaling pathway drives resistance to anti-PD-1 immunotherapy","volume":"130","author":"Theivanthiran","year":"2020","journal-title":"J Clin Invest"},{"key":"2021072117024462900_ref16","doi-asserted-by":"crossref","first-page":"3703","DOI":"10.1021\/acsnano.0c00962","article-title":"Cell-penetrating nanoparticles activate the Inflammasome to enhance antibody production by targeting microtubule-associated protein 1-light chain 3 for degradation","volume":"14","author":"Zhu","year":"2020","journal-title":"ACS Nano"},{"key":"2021072117024462900_ref17","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.tranon.2018.01.011","article-title":"A comprehensive immunologic portrait of triple-negative breast cancer","volume":"11","author":"Liu","year":"2018","journal-title":"Trans Oncol"},{"key":"2021072117024462900_ref18","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1186\/s12885-015-1880-y","article-title":"Genomic profiling of CHEK2*1100delC-mutated breast carcinomas","volume":"15","author":"Massink","year":"2015","journal-title":"BMC Cancer"},{"key":"2021072117024462900_ref19","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1126\/science.aan5951","article-title":"Genomic correlates of response to immune checkpoint therapies in clear cell renal cell carcinoma","volume":"359","author":"Miao","year":"2018","journal-title":"Science (New York, NY)"},{"key":"2021072117024462900_ref20","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/1471-2105-14-7","article-title":"GSVA: gene set variation analysis for microarray and RNA-seq data","volume":"14","author":"H\u00e4nzelmann","year":"2013","journal-title":"BMC Bioinformatics"},{"key":"2021072117024462900_ref21","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/s13073-018-0548-z","article-title":"Integrative analysis of DNA methylation and gene expression reveals hepatocellular carcinoma-specific diagnostic biomarkers","volume":"10","author":"Cheng","year":"2018","journal-title":"Genome Med"},{"key":"2021072117024462900_ref22","doi-asserted-by":"crossref","first-page":"e108","DOI":"10.1158\/0008-5472.CAN-17-0307","article-title":"TIMER: a web server for comprehensive analysis of tumor-infiltrating immune cells","volume":"77","author":"Li","year":"2017","journal-title":"Cancer Res"},{"key":"2021072117024462900_ref23","doi-asserted-by":"crossref","DOI":"10.1016\/j.immuni.2018.03.023","article-title":"The immune landscape of cancer","volume":"48","author":"Thorsson","year":"2018","journal-title":"Immunity"},{"key":"2021072117024462900_ref24","doi-asserted-by":"crossref","first-page":"2612","DOI":"10.1038\/ncomms3612","article-title":"Inferring tumour purity and stromal and immune cell admixture from expression data","volume":"4","author":"Yoshihara","year":"2013","journal-title":"Nat Commun"},{"key":"2021072117024462900_ref25","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1158\/2326-6066.CIR-16-0269","article-title":"Inflammasomes and cancer","volume":"5","author":"Karki","year":"2017","journal-title":"Cancer Immunol Res"},{"key":"2021072117024462900_ref26","doi-asserted-by":"crossref","first-page":"5400","DOI":"10.1038\/sj.onc.1205651","article-title":"DNA methylation in cancer: too much, but also too little","volume":"21","author":"Ehrlich","year":"2002","journal-title":"Oncogene"},{"key":"2021072117024462900_ref27","doi-asserted-by":"crossref","first-page":"2598","DOI":"10.1158\/1535-7163.MCT-17-0386","article-title":"Tumor mutational burden as an independent predictor of response to immunotherapy in diverse cancers","volume":"16","author":"Goodman","year":"2017","journal-title":"Mol Cancer Ther"},{"key":"2021072117024462900_ref28","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1080\/1744666X.2020.1713755","article-title":"The NLRP3 inflammasome: a therapeutic target for inflammation-associated cancers","volume":"16","author":"Gouravani","year":"2020","journal-title":"Expert Rev Clin Immunol"},{"key":"2021072117024462900_ref29","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/nm.2999","article-title":"Chemotherapy-triggered cathepsin B release in myeloid-derived suppressor cells activates the Nlrp3 inflammasome and promotes tumor growth","volume":"19","author":"Bruchard","year":"2013","journal-title":"Nat Med"},{"key":"2021072117024462900_ref30","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1111\/imm.13046","article-title":"Differential role of the NLRP3 inflammasome in infection and tumorigenesis","volume":"156","author":"Tartey","year":"2019","journal-title":"Immunology"},{"key":"2021072117024462900_ref31","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1186\/s13046-017-0589-y","article-title":"NLRP3 inflammasome activation promotes inflammation-induced carcinogenesis in head and neck squamous cell carcinoma","volume":"36","author":"Huang","year":"2017","journal-title":"J Exp Clin Cancer Res CR"},{"key":"2021072117024462900_ref32","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1002\/emmm.201201569","article-title":"Tumour inflammasome-derived IL-1\u03b2 recruits neutrophils and improves local recurrence-free survival in EBV-induced nasopharyngeal carcinoma","volume":"4","author":"Chen","year":"2012","journal-title":"EMBO Mol Med"},{"key":"2021072117024462900_ref33","doi-asserted-by":"crossref","first-page":"6477","DOI":"10.1074\/jbc.M109.064907","article-title":"Constitutively active inflammasome in human melanoma cells mediating autoinflammation via caspase-1 processing and secretion of interleukin-1beta","volume":"285","author":"Okamoto","year":"2010","journal-title":"J Biol Chem"},{"key":"2021072117024462900_ref34","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1038\/labinvest.2013.126","article-title":"Deregulation of the NLRP3 inflammasome in hepatic parenchymal cells during liver cancer progression","volume":"94","author":"Wei","year":"2014","journal-title":"Lab Invest J Tech Methods Pathol"},{"key":"2021072117024462900_ref35","doi-asserted-by":"crossref","first-page":"2126","DOI":"10.1093\/carcin\/bgs256","article-title":"Genetic variation and alterations of genes involved in NF\u03baB\/TNFAIP3- and NLRP3-inflammasome signaling affect susceptibility and outcome of colorectal cancer","volume":"33","author":"Ungerb\u00e4ck","year":"2012","journal-title":"Carcinogenesis"},{"key":"2021072117024462900_ref36","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1111\/j.1755-148X.2012.01008.x","article-title":"Inflammasome polymorphisms confer susceptibility to sporadic malignant melanoma","volume":"25","author":"Verma","year":"2012","journal-title":"Pigment Cell Melanoma Res"},{"key":"2021072117024462900_ref37","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.1084\/jem.20161707","article-title":"NLRP3 signaling drives macrophage-induced adaptive immune suppression in pancreatic carcinoma","volume":"214","author":"Daley","year":"2017","journal-title":"J Exp Med"},{"key":"2021072117024462900_ref38","doi-asserted-by":"crossref","first-page":"5393","DOI":"10.1158\/0008-5472.CAN-11-0993","article-title":"IL-18 induces PD-1-dependent immunosuppression in cancer","volume":"71","author":"Terme","year":"2011","journal-title":"Cancer Res"},{"key":"2021072117024462900_ref39","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1373\/clinchem.2019.303644","article-title":"Biomarkers for predicting response to immunotherapy with immune checkpoint inhibitors in cancer patients","volume":"65","author":"Duffy","year":"2019","journal-title":"Clin Chem"},{"key":"2021072117024462900_ref40","doi-asserted-by":"crossref","DOI":"10.1126\/science.aax0182","article-title":"Neoadjuvant checkpoint blockade for cancer immunotherapy","volume":"367","author":"Topalian","year":"2020","journal-title":"Science (New York, NY)"}],"container-title":["Briefings in Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/bib\/article-pdf\/22\/4\/bbaa345\/39138695\/bbaa345.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/bib\/article-pdf\/22\/4\/bbaa345\/39138695\/bbaa345.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,21]],"date-time":"2021-07-21T17:22:12Z","timestamp":1626888132000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bib\/article\/doi\/10.1093\/bib\/bbaa345\/5992354"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,20]]},"references-count":40,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2021,7,20]]}},"URL":"https:\/\/doi.org\/10.1093\/bib\/bbaa345","relation":{},"ISSN":["1467-5463","1477-4054"],"issn-type":[{"value":"1467-5463","type":"print"},{"value":"1477-4054","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,7]]},"published":{"date-parts":[[2020,11,20]]},"article-number":"bbaa345"}}