{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T08:48:58Z","timestamp":1791967738960,"version":"4.3.4"},"reference-count":25,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2018,1,19]],"date-time":"2018-01-19T00:00:00Z","timestamp":1516320000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100008258","name":"Hyundai Hope On Wheels","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008258","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006058","name":"St. Baldrick's Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006058","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K08CA193982"],"award-info":[{"award-number":["K08CA193982"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P30CA046934"],"award-info":[{"award-number":["P30CA046934"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2018,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>A desperate need for novel therapies in pediatric ependymoma (EPN) exists, as chemotherapy remains ineffective and radiotherapy often fails. EPN have significant infiltration of immune cells, which correlates with outcome. Immune checkpoint inhibitors provide an avenue for new treatments. This study characterizes tumor\u2010infiltrating immune cells in EPN and aims at predicting candidates for clinical trials using checkpoint inhibitors targeting PD\u2010L1\/PD\u20101 (programmed death ligand 1\/programmed death 1).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The transcriptomic profiles of the primary study cohort of EPN and other pediatric brain tumors were interrogated to identify\n                      <jats:italic>PD\u2010L1<\/jats:italic>\n                      expression levels. Transcriptomic findings were validated using the western blotting, immunohistochemistry and flow cytometry.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We evaluated\n                      <jats:italic>PD\u2010L1<\/jats:italic>\n                      mRNA expression across four intracranial subtypes of EPN in two independent cohorts and found supratentorial RELA fusion (ST\u2010RELA) tumors to have significantly higher levels. There was a correlation between high gene expression and protein PD\u2010L1 levels in ST\u2010RELA tumors by both the western blot and immunohistochemisty. The investigation of EPN cell populations revealed PD\u2010L1 was expressed on both tumor and myeloid cells in ST\u2010RELA. Other subtypes had little PD\u2010L1 in either tumor or myeloid cell compartments. Lastly, we measured PD\u20101 levels on tumor\u2010infiltrating T cells and found ST\u2010RELA tumors express PD\u20101 in both CD4 and CD8 T cells. A functional T\u2010cell exhaustion assay found ST\u2010RELA T cells to be exhausted and unable to secrete IFN\u03b3 on stimulation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings in ST\u2010RELA suggest tumor evasion and immunsuppression due to PD\u2010L1\/PD\u20101\u2010mediated T\u2010cell exhaustion. Trials of checkpoint inhibitors in EPN should be enriched for ST\u2010RELA tumors.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pbc.26960","type":"journal-article","created":{"date-parts":[[2018,1,19]],"date-time":"2018-01-19T06:15:05Z","timestamp":1516342505000},"source":"Crossref","is-referenced-by-count":58,"title":["Specific expression of PD\u2010L1 in RELA\u2010fusion supratentorial ependymoma: Implications for PD\u20101\u2010targeted therapy"],"prefix":"10.1002","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6762-9610","authenticated-orcid":false,"given":"Davis A.","family":"Witt","sequence":"first","affiliation":[{"name":"Department of Pediatrics University of Colorado Denver  Aurora Colorado"},{"name":"Morgan Adams Foundation Pediatric Brain Tumor Research Program Children's Hospital Colorado  Aurora Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew M.","family":"Donson","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Colorado Denver  Aurora Colorado"},{"name":"Morgan Adams Foundation Pediatric Brain Tumor Research Program Children's Hospital Colorado  Aurora Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir","family":"Amani","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Colorado Denver  Aurora Colorado"},{"name":"Morgan Adams Foundation Pediatric Brain Tumor Research Program Children's Hospital Colorado  Aurora Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel C.","family":"Moreira","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Colorado Denver  Aurora Colorado"},{"name":"Morgan Adams Foundation Pediatric Brain Tumor Research Program Children's Hospital Colorado  Aurora Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bridget","family":"Sanford","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Colorado Denver  Aurora Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsey M.","family":"Hoffman","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Colorado Denver  Aurora Colorado"},{"name":"Morgan Adams Foundation Pediatric Brain Tumor Research Program Children's Hospital Colorado  Aurora Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael H.","family":"Handler","sequence":"additional","affiliation":[{"name":"Morgan Adams Foundation Pediatric Brain Tumor Research Program Children's Hospital Colorado  Aurora Colorado"},{"name":"Department of Neurosurgery University of Colorado Denver  Aurora Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean M. Mulcahy","family":"Levy","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Colorado Denver  Aurora Colorado"},{"name":"Morgan Adams Foundation Pediatric Brain Tumor Research Program Children's Hospital Colorado  Aurora Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth L.","family":"Jones","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Colorado Denver  Aurora Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anandani","family":"Nellan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Colorado Denver  Aurora Colorado"},{"name":"Morgan Adams Foundation Pediatric Brain Tumor Research Program Children's Hospital Colorado  Aurora Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas K.","family":"Foreman","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Colorado Denver  Aurora Colorado"},{"name":"Morgan Adams Foundation Pediatric Brain Tumor Research Program Children's Hospital Colorado  Aurora Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea M.","family":"Griesinger","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Colorado Denver  Aurora Colorado"},{"name":"Morgan Adams Foundation Pediatric Brain Tumor Research Program Children's Hospital Colorado  Aurora Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,1,19]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.5732\/cjc.011.10129"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13109"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2015.04.002"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI80011"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2017.00141"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hemonc.2013.09.005"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-13-3271"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-16-0698"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1301966"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-013-1212-8"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13954"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-15-0061"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/nox061"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2015.02.018"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2009.00333.x"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0902811"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2015.65.7825"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12929-017-0329-9"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12477"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-16-0903"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2016.05.021"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0123410"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.2147\/OTT.S105862"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.5414\/NP300988"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2017.74.7642"}],"container-title":["Pediatric Blood &amp; Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpbc.26960","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pbc.26960","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,24]],"date-time":"2023-09-24T05:53:18Z","timestamp":1695534798000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pbc.26960"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,1,19]]},"references-count":25,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2018,5]]}},"alternative-id":["10.1002\/pbc.26960"],"URL":"https:\/\/doi.org\/10.1002\/pbc.26960","archive":["Portico"],"relation":{},"ISSN":["1545-5009","1545-5017"],"issn-type":[{"value":"1545-5009","type":"print"},{"value":"1545-5017","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,1,19]]},"article-number":"e26960"}}