Assessment of Programmed Death-Ligand 1 Expression and Tumor-Associated Immune Cells in Pediatric Cancer Tissues

作者：Majzner Robbie G; Simon Jason S; Grosso Joseph F; Martinez Daniel; Pawel Bruce R; Santi Mariarita; Merchant Melinda S; Geoerger Birgit; Hezam Imene; Marty Virginie; Vielh Phillippe; Daugaard Mads; Sorensen Poul H; Mackall Crystal L; Maris John M

来源：Cancer, 2017, 123(19): 3807-3815.

DOI：10.1002/cncr.30724

• checkpoint
• immunotherapy
• neuroblastoma
• pediatric cancer
• programmed death 1/programmed death 1 ligand (PD-1/PD-L1) blockade
• tumor-infiltrating lymphocytes

BACKGROUND: Programmed death 1 (PD-1) signaling in the tumor microenvironment dampens immune responses to cancer, and blocking this axis induces antitumor effects in several malignancies. Clinical studies of PD-1 blockade are only now being initiated in pediatric patients, and little is known regarding programmed death-ligand 1 (PD-L1) expression in common childhood cancers. The authors characterized PD-L1 expression and tumor-associated immune cells (TAICs) (lymphocytes and macrophages) in common pediatric cancers. METHODS: Whole slide sections and tissue microarrays were evaluated by immunohistochemistry for PD-L1 expression and for the presence of TAICs. TAICs were also screened for PD-L1 expression. RESULTS: Thirty-nine of 451 evaluable tumors (9%) expressed PD-L1 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-L1 staining was associated with inferior survival among patients with neuroblastoma (P = .004). Seventy-four percent of tumors contained lymphocytes and/or macrophages. Macrophages were significantly more likely to be identified in PD-L1-positive versus PD-L1-negative tumors (P < .001). CONCLUSIONS: A subset of diagnostic pediatric cancers exhibit PD-L1 expression, whereas a much larger fraction demonstrates infiltration with tumor-associated lymphocytes. PD-L1 expression may be a biomarker for poor outcome in neuroblastoma. Further preclinical and clinical investigation will define the predictive nature of PD-L1 expression in childhood cancers both at diagnosis and after exposure to chemoradiotherapy.

• 出版日期2017-10-1