This study sought to evaluate expression of PD-L1 and HLA class I on neuroblastoma cells and PD-1 and LAG3 on tumor-infiltrating lymphocytes to better define patient risk-stratification and understand whether this tumor may benefit from therapies targeting immune-checkpoint molecules. Experimental Design: In situ immunohistochemical staining for PD-L1, HLA class I, PD-1 and LAG3 was assessed in 77 neuroblastoma specimens, previously characterized for tumor-infiltrating T cell-density, and correlated with clinical outcome. Surface expression of PD-L1 was evaluated by flow-cytometry and immunohistochemistry in neuroblastoma cell lines and tumors genetically and/or pharmacologically inhibited for MYC and MYCN. A dataset of 477 human primary neuroblastomas from GEO and ArrayExpress databases was explored for PD-L1, MYC and MYCN correlation. Results: Multivariate Cox regression analysis demonstrated that the combination of PD-L1 and HLA class I tumor-cell density is a prognostic biomarker for predicting overall survival in neuroblastoma patients (p=0.0448). MYC and MYCN control the expression of PD-L1 in neuroblastoma cells both in vitro and in vivo. Consistently, abundance of PD-L1 transcript correlates with MYC expression in primary neuroblastoma. Conclusions: The combination of PD-L1 and HLA class I represents a novel prognostic biomarker for neuroblastoma. Pharmacological inhibition of MYCN and MYC may be exploited to target PD-L1 and restore an efficient anti-tumor immunity in high-risk neuroblastoma.
|Titolo:||PD-L1 is a therapeutic target of the Bromodomain inhibitor JQ1 and, combined with HLA class I, a promising prognostic biomarker in neuroblastoma|
|Autori interni:||Mina, Marco|
|Data di pubblicazione:||2017|
|Rivista:||CLINICAL CANCER RESEARCH|
|Appare nelle tipologie:||1.1 Articolo in rivista|
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