{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T00:46:39Z","timestamp":1744850799599,"version":"3.37.3"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"D1","license":[{"start":{"date-parts":[[2020,10,3]],"date-time":"2020-10-03T00:00:00Z","timestamp":1601683200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014219","name":"National Science Fund for Distinguished Young Scholars","doi-asserted-by":"publisher","award":["NSFC-81925032"],"id":[{"id":"10.13039\/501100014219","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81974456"],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,1,8]]},"abstract":"Abstract<\/jats:title>Tumor-infiltrating immune cells as integral component of the tumor microenvironment are associated with tumor progress, prognosis and responses to immunotherapy. Genetic variants have been demonstrated to impact tumor-infiltrating, underscoring the heritable character of immune landscape. Therefore, identification of immunity quantitative trait loci (immunQTLs), which evaluate the effect of genetic variants on immune cells infiltration, might present a critical step toward fully understanding the contribution of genetic variants in tumor development. Although emerging studies have demonstrated the determinants of germline variants on immune infiltration, no database has yet been developed to systematically analyze immunQTLs across multiple cancer types. Using genotype data from TCGA database and immune cell fractions estimated by CIBERSORT, we developed a computational pipeline to identify immunQTLs in 33 cancer types. A total of 913 immunQTLs across different cancer types were identified. Among them, 5 immunQTLs are associated with patient overall survival. Furthermore, by integrating immunQTLs with GWAS data, we identified 527 immunQTLs overlapping with known GWAS linkage disequilibrium regions. Finally, we constructed a user-friendly database, CancerImmunityQTL (http:\/\/www.cancerimmunityqtl-hust.com\/) for users to browse, search and download data of interest. This database provides an informative resource to understand the germline determinants of immune infiltration in human cancer and benefit from personalized cancer immunotherapy.<\/jats:p>","DOI":"10.1093\/nar\/gkaa805","type":"journal-article","created":{"date-parts":[[2020,9,17]],"date-time":"2020-09-17T19:24:43Z","timestamp":1600370683000},"page":"D1065-D1073","source":"Crossref","is-referenced-by-count":30,"title":["CancerImmunityQTL: a database to systematically evaluate the impact of genetic variants on immune infiltration in human cancer"],"prefix":"10.1093","volume":"49","author":[{"given":"Jianbo","family":"Tian","sequence":"first","affiliation":[{"name":"Department of Epidemiology and Biostatistics, Key Laboratory of Environmental Health of Ministry of Education, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}]},{"given":"Yimin","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, Key Laboratory of Environmental Health of Ministry of Education, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}]},{"given":"Yue","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, Key Laboratory of Environmental Health of Ministry of Education, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}]},{"given":"Zequn","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, Key Laboratory of Environmental Health of Ministry of Education, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}]},{"given":"Jinyu","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, Key Laboratory of Environmental Health of Ministry of Education, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}]},{"given":"Yao","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, Key Laboratory of Environmental Health of Ministry of Education, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}]},{"given":"Nan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, Key Laboratory of Environmental Health of Ministry of Education, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}]},{"given":"Xiaoyang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, Key Laboratory of Environmental Health of Ministry of Education, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}]},{"given":"Pingting","family":"Ying","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, Key Laboratory of Environmental Health of Ministry of Education, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}]},{"given":"Shanshan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, Key Laboratory of Environmental Health of Ministry of Education, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}]},{"given":"Ying","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, Key Laboratory of Environmental Health of Ministry of Education, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}]},{"given":"Huilan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}]},{"given":"Rong","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, Key Laboratory of Environmental Health of Ministry of Education, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}]},{"given":"Jiang","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, Key Laboratory of Environmental Health of Ministry of Education, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4641-0262","authenticated-orcid":false,"given":"Xiaoping","family":"Miao","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, Key Laboratory of Environmental Health of Ministry of Education, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}]}],"member":"286","published-online":{"date-parts":[[2020,10,3]]},"reference":[{"key":"2021010313121005800_B1","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1016\/j.ccell.2018.07.009","article-title":"Notch signaling in the tumor microenvironment","volume":"34","author":"Meurette","year":"2018","journal-title":"Cancer Cell"},{"key":"2021010313121005800_B2","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1038\/nri3902","article-title":"Immunological hallmarks of stromal cells in the tumour microenvironment","volume":"15","author":"Turley","year":"2015","journal-title":"Nat. Rev. Immunol."},{"key":"2021010313121005800_B3","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1038\/nrc3245","article-title":"The immune contexture in human tumours: impact on clinical outcome","volume":"12","author":"Fridman","year":"2012","journal-title":"Nat. Rev. Cancer"},{"key":"2021010313121005800_B4","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1038\/nm.3909","article-title":"The prognostic landscape of genes and infiltrating immune cells across human cancers","volume":"21","author":"Gentles","year":"2015","journal-title":"Nat. Med."},{"key":"2021010313121005800_B5","doi-asserted-by":"crossref","first-page":"101296","DOI":"10.1016\/j.isci.2020.101296","article-title":"Immune cell associations with cancer risk","volume":"23","author":"Palomero","year":"2020","journal-title":"iScience"},{"key":"2021010313121005800_B6","doi-asserted-by":"crossref","first-page":"E11701","DOI":"10.1073\/pnas.1804506115","article-title":"Germline genetic polymorphisms influence tumor gene expression and immune cell infiltration","volume":"115","author":"Lim","year":"2018","journal-title":"Proc. Natl Acad. Sci. U.S.A."},{"key":"2021010313121005800_B7","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1056\/NEJM200007133430201","article-title":"Environmental and heritable factors in the causation of cancer\u2013analyses of cohorts of twins from Sweden, Denmark, and Finland","volume":"343","author":"Lichtenstein","year":"2000","journal-title":"N. Engl. J. Med."},{"key":"2021010313121005800_B8","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1038\/s41591-020-0879-3","article-title":"Common germline variants of the human APOE gene modulate melanoma progression and survival","volume":"26","author":"Ostendorf","year":"2020","journal-title":"Nat. Med."},{"key":"2021010313121005800_B9","doi-asserted-by":"crossref","first-page":"1804","DOI":"10.1158\/0008-5472.CAN-19-2389","article-title":"Risk SNP-Mediated Enhancer-Promoter interaction drives colorectal cancer through both FADS2 and AP002754.2","volume":"80","author":"Tian","year":"2020","journal-title":"Cancer Res."},{"key":"2021010313121005800_B10","doi-asserted-by":"crossref","first-page":"9362","DOI":"10.1073\/pnas.0903103106","article-title":"Potential etiologic and functional implications of genome-wide association loci for human diseases and traits","volume":"106","author":"Hindorff","year":"2009","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021010313121005800_B11","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1038\/s41576-019-0127-1","article-title":"Benefits and limitations of genome-wide association studies","volume":"20","author":"Tam","year":"2019","journal-title":"Nat. Rev. Genet."},{"key":"2021010313121005800_B12","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.ajhg.2019.05.004","article-title":"Systematic functional interrogation of genes in GWAS loci identified ATF1 as a key driver in colorectal cancer modulated by a Promoter-Enhancer interaction","volume":"105","author":"Tian","year":"2019","journal-title":"Am. J. Hum. Genet."},{"key":"2021010313121005800_B13","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/ng.3538","article-title":"Integration of summary data from GWAS and eQTL studies predicts complex trait gene targets","volume":"48","author":"Zhu","year":"2016","journal-title":"Nat. Genet."},{"key":"2021010313121005800_B14","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1111\/cge.13187","article-title":"Genetic association of molecular traits: A help to identify causative variants in complex diseases","volume":"93","author":"Vandiedonck","year":"2018","journal-title":"Clin. Genet."},{"key":"2021010313121005800_B15","doi-asserted-by":"crossref","first-page":"D909","DOI":"10.1093\/nar\/gky954","article-title":"CancerSplicingQTL: a database for genome-wide identification of splicing QTLs in human cancer","volume":"47","author":"Tian","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"2021010313121005800_B16","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.cell.2013.08.041","article-title":"Genetic variants regulating immune cell levels in health and disease","volume":"155","author":"Orru","year":"2013","journal-title":"Cell"},{"key":"2021010313121005800_B17","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1038\/s41590-018-0049-7","article-title":"Natural variation in the parameters of innate immune cells is preferentially driven by genetic factors","volume":"19","author":"Patin","year":"2018","journal-title":"Nat. Immunol."},{"key":"2021010313121005800_B18","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1093\/jnci\/djt051","article-title":"Genome-wide association study of susceptibility loci for cervical cancer","volume":"105","author":"Chen","year":"2013","journal-title":"J. Natl. Cancer Inst."},{"key":"2021010313121005800_B19","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1038\/clpt.2014.89","article-title":"Inflammation-related genetic variations and survival in patients with advanced non-small cell lung cancer receiving first-line chemotherapy","volume":"96","author":"Pu","year":"2014","journal-title":"Clin. Pharmacol. Ther."},{"key":"2021010313121005800_B20","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/j.ccell.2020.06.002","article-title":"Immunogenomic landscape of hematological malignancies","volume":"38","author":"Dufva","year":"2020","journal-title":"Cancer Cell"},{"key":"2021010313121005800_B21","doi-asserted-by":"crossref","first-page":"2900","DOI":"10.1016\/j.celrep.2020.02.039","article-title":"Germline features associated with immune infiltration in solid tumors","volume":"30","author":"Shahamatdar","year":"2020","journal-title":"Cell Rep."},{"key":"2021010313121005800_B22","doi-asserted-by":"crossref","first-page":"e000336","DOI":"10.1136\/jitc-2019-000336","article-title":"Genetic associations of T cell cancer immune response-related genes with T cell phenotypes and clinical outcomes of early-stage lung cancer","volume":"8","author":"Wang","year":"2020","journal-title":"J. Immunother. Cancer"},{"key":"2021010313121005800_B23","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1007\/s00262-018-2150-z","article-title":"Quantifying tumor-infiltrating immune cells from transcriptomics data","volume":"67","author":"Finotello","year":"2018","journal-title":"Cancer Immunol. Immunother."},{"key":"2021010313121005800_B24","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1038\/nmeth.3337","article-title":"Robust enumeration of cell subsets from tissue expression profiles","volume":"12","author":"Newman","year":"2015","journal-title":"Nat. Methods"},{"key":"2021010313121005800_B25","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1126\/science.1262110","article-title":"Human genomics. The Genotype-Tissue Expression (GTEx) pilot analysis: multitissue gene regulation in humans","volume":"348","author":"Consortium","year":"2015","journal-title":"Science"},{"key":"2021010313121005800_B26","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1186\/s13059-016-0926-z","article-title":"Systematic identification of genetic influences on methylation across the human life course","volume":"17","author":"Gaunt","year":"2016","journal-title":"Genome Biol."},{"key":"2021010313121005800_B27","doi-asserted-by":"crossref","first-page":"D971","DOI":"10.1093\/nar\/gkx861","article-title":"PancanQTL: systematic identification of cis-eQTLs and trans-eQTLs in 33 cancer types","volume":"46","author":"Gong","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"2021010313121005800_B28","doi-asserted-by":"crossref","first-page":"e1000529","DOI":"10.1371\/journal.pgen.1000529","article-title":"A flexible and accurate genotype imputation method for the next generation of genome-wide association studies","volume":"5","author":"Howie","year":"2009","journal-title":"PLoS Genet."},{"key":"2021010313121005800_B29","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1038\/ng.2653","article-title":"The Genotype-Tissue Expression (GTEx) project","volume":"45","author":"Consortium","year":"2013","journal-title":"Nat. Genet."},{"key":"2021010313121005800_B30","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s13742-015-0047-8","article-title":"Second-generation PLINK: rising to the challenge of larger and richer datasets","volume":"4","author":"Chang","year":"2015","journal-title":"Gigascience"},{"key":"2021010313121005800_B31","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1038\/nprot.2011.457","article-title":"Using probabilistic estimation of expression residuals (PEER) to obtain increased power and interpretability of gene expression analyses","volume":"7","author":"Stegle","year":"2012","journal-title":"Nat. Protoc."},{"key":"2021010313121005800_B32","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1038\/nature13602","article-title":"Putative cis-regulatory drivers in colorectal cancer","volume":"512","author":"Ongen","year":"2014","journal-title":"Nature"},{"key":"2021010313121005800_B33","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1038\/s41467-017-01818-4","article-title":"Genome-wide mapping of genetic determinants influencing DNA methylation and gene expression in human hippocampus","volume":"8","author":"Schulz","year":"2017","journal-title":"Nat. Commun."},{"key":"2021010313121005800_B34","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1093\/bioinformatics\/bts163","article-title":"Matrix eQTL: ultra fast eQTL analysis via large matrix operations","volume":"28","author":"Shabalin","year":"2012","journal-title":"Bioinformatics"},{"key":"2021010313121005800_B35","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1126\/science.1232227","article-title":"Neutralizing tumor-promoting chronic inflammation: a magic bullet","volume":"339","author":"Coussens","year":"2013","journal-title":"Science"},{"key":"2021010313121005800_B36","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the false Discovery Rate: A practical and powerful approach to multiple testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J. Roy. Statist. Soc.: Ser. B (Methodological)"},{"key":"2021010313121005800_B37","doi-asserted-by":"crossref","first-page":"D896","DOI":"10.1093\/nar\/gkw1133","article-title":"The new NHGRI-EBI Catalog of published genome-wide association studies (GWAS Catalog)","volume":"45","author":"MacArthur","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"2021010313121005800_B38","doi-asserted-by":"crossref","first-page":"2938","DOI":"10.1093\/bioinformatics\/btn564","article-title":"SNAP: a web-based tool for identification and annotation of proxy SNPs using HapMap","volume":"24","author":"Johnson","year":"2008","journal-title":"Bioinformatics"},{"key":"2021010313121005800_B39","doi-asserted-by":"crossref","first-page":"80","DOI":"10.4161\/fly.19695","article-title":"A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff: SNPs in the genome of Drosophila melanogaster strain w1118; iso-2; iso-3","volume":"6","author":"Cingolani","year":"2012","journal-title":"Fly (Austin)"},{"key":"2021010313121005800_B40","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1038\/s41588-019-0472-1","article-title":"Mapping cis-regulatory chromatin contacts in neural cells links neuropsychiatric disorder risk variants to target genes","volume":"51","author":"Song","year":"2019","journal-title":"Nat. Genet."},{"key":"2021010313121005800_B41","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1038\/nature07205","article-title":"Cancer-related inflammation","volume":"454","author":"Mantovani","year":"2008","journal-title":"Nature"}],"container-title":["Nucleic Acids Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/nar\/article-pdf\/49\/D1\/D1065\/35363719\/gkaa805.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/nar\/article-pdf\/49\/D1\/D1065\/35363719\/gkaa805.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,14]],"date-time":"2024-08-14T02:08:46Z","timestamp":1723601326000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/nar\/article\/49\/D1\/D1065\/5917653"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,3]]},"references-count":41,"journal-issue":{"issue":"D1","published-online":{"date-parts":[[2020,10,3]]},"published-print":{"date-parts":[[2021,1,8]]}},"URL":"https:\/\/doi.org\/10.1093\/nar\/gkaa805","relation":{},"ISSN":["0305-1048","1362-4962"],"issn-type":[{"type":"print","value":"0305-1048"},{"type":"electronic","value":"1362-4962"}],"subject":[],"published-other":{"date-parts":[[2021,1,8]]},"published":{"date-parts":[[2020,10,3]]}}}