{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T17:46:36Z","timestamp":1792172796686,"version":"4.4.0"},"reference-count":41,"publisher":"American Society for Clinical Investigation","issue":"12","license":[{"start":{"date-parts":[[2022,6,22]],"date-time":"2022-06-22T00:00:00Z","timestamp":1655856000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["P30 CA016672"],"award-info":[{"award-number":["P30 CA016672"]}]},{"name":"NIH","award":["R37CA214800"],"award-info":[{"award-number":["R37CA214800"]}]},{"name":"NIH","award":["CA18689204"],"award-info":[{"award-number":["CA18689204"]}]},{"name":"NIH","award":["CA1208113"],"award-info":[{"award-number":["CA1208113"]}]},{"DOI":"10.13039\/100008222","name":"Ben and Catherine Ivy Foundation","doi-asserted-by":"crossref","award":["Heimberger"],"award-info":[{"award-number":["Heimberger"]}],"id":[{"id":"10.13039\/100008222","id-type":"DOI","asserted-by":"crossref"}]},{"name":"The University of Texas MD Anderson Cancer Center GBM Moonshot","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"the Brockman Foundation","award":["Heimberger"],"award-info":[{"award-number":["Heimberger"]}]},{"DOI":"10.13039\/100006064","name":"Sontag Foundation","doi-asserted-by":"crossref","award":["Jian Hu Lab"],"award-info":[{"award-number":["Jian Hu Lab"]}],"id":[{"id":"10.13039\/100006064","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,6,22]]},"abstract":"<jats:p>\n                    Novel therapeutic strategies targeting glioblastoma (GBM) often fail in the clinic, partly because preclinical models in which hypotheses are being tested do not recapitulate human disease. To address this challenge, we took advantage of our previously developed spontaneous\n                    <jats:italic>Qk\/Trp53\/Pten<\/jats:italic>\n                    (QPP) triple-knockout model of human GBM, comparing the immune microenvironment of QPP mice with that of patient-derived tumors to determine whether this model provides opportunity for gaining insights into tumor physiopathology and preclinical evaluation of therapeutic agents. Immune profiling analyses and single-cell sequencing of implanted and spontaneous tumors from QPP mice and from patients with glioma revealed intratumoral immune components that were predominantly myeloid cells (e.g., monocytes, macrophages, and microglia), with minor populations of T, B, and NK cells. When comparing spontaneous and implanted mouse samples, we found more neutrophils and T and NK cells in the implanted model. Neutrophils and T and NK cells were increased in abundance in samples derived from human high-grade glioma compared with those derived from low-grade glioma. Overall, our data demonstrate that our implanted and spontaneous QPP models recapitulate the immunosuppressive myeloid-dominant nature of the tumor microenvironment of human gliomas. Our model provides a suitable tool for investigating the complex immune compartment of gliomas.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.148990","type":"journal-article","created":{"date-parts":[[2022,6,6]],"date-time":"2022-06-06T09:26:16Z","timestamp":1654507576000},"source":"Crossref","is-referenced-by-count":31,"title":["Immune landscape of a genetically engineered murine model of glioma compared with human glioma"],"prefix":"10.1172","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0375-8119","authenticated-orcid":true,"given":"Daniel B.","family":"Zamler","sequence":"first","affiliation":[{"name":"Department of Genomic Medicine,"},{"name":"Department of Cancer Biology, and"},{"name":"UT Health Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Shingu","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6679-7599","authenticated-orcid":true,"given":"Laura M.","family":"Kahn","sequence":"additional","affiliation":[{"name":"UT Health Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA."},{"name":"Department of Immunology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7211-8986","authenticated-orcid":true,"given":"Kristin","family":"Huntoon","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia","family":"Kassab","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Ott","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna","family":"Tomczak","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6609-9777","authenticated-orcid":true,"given":"Jintan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine,"},{"name":"UT Health Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yating","family":"Li","sequence":"additional","affiliation":[{"name":"UT Health Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA."},{"name":"Department of Melanoma Medical Oncology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivy","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Melanoma Medical Oncology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rocio","family":"Zorilla-Veloz","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, and"},{"name":"UT Health Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4429-7307","authenticated-orcid":true,"given":"Cassian","family":"Yee","sequence":"additional","affiliation":[{"name":"UT Health Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA."},{"name":"Department of Melanoma Medical Oncology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2321-6894","authenticated-orcid":true,"given":"Kunal","family":"Rai","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine,"},{"name":"UT Health Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6890-8355","authenticated-orcid":true,"given":"Betty Y.S.","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1969-659X","authenticated-orcid":true,"given":"Stephanie S.","family":"Watowich","sequence":"additional","affiliation":[{"name":"UT Health Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA."},{"name":"Department of Immunology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9970-8695","authenticated-orcid":true,"given":"Amy B.","family":"Heimberger","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, Lou and Jean Malnati Brain Tumor Institute, Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5225-9610","authenticated-orcid":true,"given":"Giulio F.","family":"Draetta","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine,"},{"name":"UT Health Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9760-2013","authenticated-orcid":true,"given":"Jian","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, and"},{"name":"UT Health Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2022,6,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.2004088"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.09.030"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-17-1846"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0135-2"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-017-0424-2"},{"key":"B6","article-title":"Window-of-opportunity clinical trial of a PD-1 inhibitor in patients with recurrent glioblastoma","author":"De Groot","journal-title":"J Clin Oncol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-16-0156"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2018.1501137"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3711"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2009.12.020"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-12-0095"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/ng0396-260"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-22782-0"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.60467"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1172\/JCI131800"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20190348"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.09.034"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1101\/gad.189001.112"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3500"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-016-1539-z"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/ng.806"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1101\/gr.107524.110"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2514"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1002\/0471250953.bi1110s43"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1215\/15228517-2006-008"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.5.2731"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1222738110"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1038\/nature13992"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01004"},{"key":"B30","unstructured":"Chen S. Gene Ontologies of scSeq Data. 2020. https:\/\/github.com\/chansigit\/scSnippet Accessed May 12, 2022"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.04.055"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.05.007"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1126\/science.aai8478"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.2006.00208.x"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2005.07.689"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-017-2626-2"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.4096"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.05.031"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-019-1874-1"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.3171\/jns.1991.75.6.0922"},{"issue":"5","key":"B41","first-page":"467","article-title":"Tissue culture studies of the glioblastoma multiforme","volume":"5","author":"Buckely","year":"1929","journal-title":"Am J Pathol"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/148990\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T23:32:45Z","timestamp":1779147165000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/148990"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,22]]},"references-count":41,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2022,6,22]]},"published-print":{"date-parts":[[2022,6,22]]}},"alternative-id":["10.1172\/jci.insight.148990"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.148990","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,22]]},"article-number":"e148990"}}