PD-L1 and CD8+PD1+ lymphocytes exist as targets in the pediatric tumor microenvironment for immunomodulatory therapy
| Autor: | Ferdousi Chowdhury, Toby Mellows, Simon Mitchell, Stuart N. Dunn, Juliet C. Gray, Margaret Ashton-Key |
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| Rok vydání: | 2015 |
| Předmět: |
Pathology
medicine.medical_specialty medicine.medical_treatment Immunology Immunotherapy Biology medicine.disease Oncology Neuroblastoma PD-L1 medicine Cancer research biology.protein Alveolar rhabdomyosarcoma Immunology and Allergy Immunohistochemistry Osteosarcoma Embryonal rhabdomyosarcoma Sarcoma |
| Zdroj: | OncoImmunology. 4:e1029701 |
| ISSN: | 2162-402X |
| Popis: | Recent monoclonal antibody trials targeting the PD1/PD-L1 immune-checkpoint pathway have shown remarkable success in treating adult malignancies, with PD-L1-expressing tumors showing the most objective response. However, little is known as to whether pediatric cancers have also adopted this immune evasion mechanism. We evaluated 115 pediatric tumors (taken at diagnosis) for PD-L1 expression and the presence of CD8+ tumor-infiltrating lymphocytes (TILs). Tumors with >5% PD-L1 membrane staining were scored positive. The presence of CD8+ TILs expressing PD-1 was assessed using dual-labeling immunohistochemistry. Data were evaluated against clinical demographics. The proportion of PD-L1+ tumors was 86% for alveolar rhabdomyosarcoma (12/14), 72% for high-risk neuroblastoma (31/43), 57% for Ewing's sarcoma (8/14), 50% for embryonal rhabdomyosarcoma (8/16) and 47% for osteosarcoma (7/15). Increased proportions of CD8+ TILs significantly correlated with PD-1 expression. When grouped by cancer type, those with the... |
| Databáze: | OpenAIRE |
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