{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T21:24:38Z","timestamp":1790717078987,"version":"4.1.0"},"reference-count":65,"publisher":"Wiley","issue":"19","license":[{"start":{"date-parts":[[2017,6,13]],"date-time":"2017-06-13T00:00:00Z","timestamp":1497312000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100002491","name":"Bristol-Myers Squibb","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002491","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009730","name":"Stand Up To Cancer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009730","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006058","name":"St. Baldrick's Foundation","doi-asserted-by":"publisher","award":["SU2C\u2010AACR\u2010DT1113"],"award-info":[{"award-number":["SU2C\u2010AACR\u2010DT1113"]}],"id":[{"id":"10.13039\/100006058","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2017,10]]},"abstract":"<jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Programmed death 1 (PD\u20101) signaling in the tumor microenvironment dampens immune responses to cancer, and blocking this axis induces antitumor effects in several malignancies. Clinical studies of PD\u20101 blockade are only now being initiated in pediatric patients, and little is known regarding programmed death\u2010ligand 1 (PD\u2010L1) expression in common childhood cancers. The authors characterized PD\u2010L1 expression and tumor\u2010associated immune cells (TAICs) (lymphocytes and macrophages) in common pediatric cancers.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>Whole slide sections and tissue microarrays were evaluated by immunohistochemistry for PD\u2010L1 expression and for the presence of TAICs. TAICs were also screened for PD\u2010L1 expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Thirty\u2010nine of 451 evaluable tumors (9%) expressed PD\u2010L1 in at least 1% of tumor cells. The highest frequency histotypes comprised Burkitt lymphoma (80%; 8 of 10 tumors), glioblastoma multiforme (36%; 5 of 14 tumors), and neuroblastoma (14%; 17 of 118 tumors). PD\u2010L1 staining was associated with inferior survival among patients with neuroblastoma (<jats:italic>P<\/jats:italic>\u2009=\u2009.004). Seventy\u2010four percent of tumors contained lymphocytes and\/or macrophages. Macrophages were significantly more likely to be identified in PD\u2010L1\u2013positive versus PD\u2010L1\u2013negative tumors (<jats:italic>P<\/jats:italic>\u2009&lt;\u2009.001).<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>A subset of diagnostic pediatric cancers exhibit PD\u2010L1 expression, whereas a much larger fraction demonstrates infiltration with tumor\u2010associated lymphocytes. PD\u2010L1 expression may be a biomarker for poor outcome in neuroblastoma. Further preclinical and clinical investigation will define the predictive nature of PD\u2010L1 expression in childhood cancers both at diagnosis and after exposure to chemoradiotherapy. <jats:bold><jats:italic>Cancer<\/jats:italic> 2017;123:3807\u20133815.<\/jats:bold> \u00a9 <jats:italic>2017 American Cancer Society<\/jats:italic><\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.30724","type":"journal-article","created":{"date-parts":[[2017,6,13]],"date-time":"2017-06-13T10:22:43Z","timestamp":1497349363000},"page":"3807-3815","source":"Crossref","is-referenced-by-count":168,"title":["Assessment of programmed death\u2010ligand 1 expression and tumor\u2010associated immune cells in pediatric cancer tissues"],"prefix":"10.1002","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6969-8011","authenticated-orcid":false,"given":"Robbie G.","family":"Majzner","sequence":"first","affiliation":[{"name":"Department of Pediatrics Stanford University Stanford California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason S.","family":"Simon","sequence":"additional","affiliation":[{"name":"Bristol\u2010Myers Squibb Princeton New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph F.","family":"Grosso","sequence":"additional","affiliation":[{"name":"Bristol\u2010Myers Squibb Princeton New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Martinez","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Children's Hospital of Philadelphia Philadelphia Pennsylvania"},{"name":"Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce R.","family":"Pawel","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Children's Hospital of Philadelphia Philadelphia Pennsylvania"},{"name":"Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariarita","family":"Santi","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Children's Hospital of Philadelphia Philadelphia Pennsylvania"},{"name":"Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melinda S.","family":"Merchant","sequence":"additional","affiliation":[{"name":"Pediatric Oncology Branch, National Cancer Institute Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgit","family":"Geoerger","sequence":"additional","affiliation":[{"name":"Department of Pediatric and Adolescent Medicine Gustave Roussy Institute Villejuif France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imene","family":"Hezam","sequence":"additional","affiliation":[{"name":"Department of Pediatric and Adolescent Medicine Gustave Roussy Institute Villejuif France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginie","family":"Marty","sequence":"additional","affiliation":[{"name":"Department of Medical Biology and Pathology Gustave Roussy Institute Villejuif France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillippe","family":"Vielh","sequence":"additional","affiliation":[{"name":"Department of Medical Biology and Pathology Gustave Roussy Institute Villejuif France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mads","family":"Daugaard","sequence":"additional","affiliation":[{"name":"Vancouver Prostate Center Vancouver British Columbia Canada"},{"name":"Department of Urologic Sciences University of British Columbia Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Poul H.","family":"Sorensen","sequence":"additional","affiliation":[{"name":"British Columbia Cancer Agency Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Crystal L.","family":"Mackall","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Stanford University Stanford California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M.","family":"Maris","sequence":"additional","affiliation":[{"name":"Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania"},{"name":"Department of Pediatrics University of Pennsylvania Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,6,13]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2015.03.007"},{"key":"e_1_2_8_3_1","unstructured":"Bristol\u2010Myers Squibb.YERVOY [package insert]. 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