Supplementary Figure S3 from PD-L1 Is a Therapeutic Target of the Bromodomain Inhibitor JQ1 and, Combined with HLA Class I, a Promising Prognostic Biomarker in Neuroblastoma

Melaiu, Ombretta; Mina, Marco; Chierici, Marco; Boldrini, Renata; Jurman, Giuseppe; Romania, Paolo; D'Alicandro, Valerio; Benedetti, Maria C.; Castellano, Aurora; Liu, Tao; Furlanello, Cesare; Locatelli, Franco; Fruci, Doriana

doi:10.1158/1078-0432.22469168.v1

Supplementary Figure S3 from PD-L1 Is a Therapeutic Target of the Bromodomain Inhibitor JQ1 and, Combined with HLA Class I, a Promising Prognostic Biomarker in Neuroblastoma

journal contribution

posted on 2023-03-31, 20:32 authored by Ombretta Melaiu, Marco Mina, Marco Chierici, Renata Boldrini, Giuseppe Jurman, Paolo Romania, Valerio D'Alicandro, Maria C. Benedetti, Aurora Castellano, Tao Liu, Cesare Furlanello, Franco Locatelli, Doriana Fruci

<p>This figure includes Kaplan-Meier curves of RFS (A, C and E) and EFS (B, D and F) according to the density of the combined PD-L1+ and HLA-I+ tumor-cell densities with tumor infiltrating CD3+ T cells (A and B), tumor infiltrating CD4+ T cells (C and D), and tumor infiltrating CD8+ T cells (E and F).</p>

Funding

AIRC

Italian Ministry of Health

Fondazione Italiana per la Lotta al Neuroblastoma

Fondazione Umberto Veronesi

History

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1.
DOI - Is supplement to PD-L1 Is a Therapeutic Target of the Bromodomain Inhibitor JQ1 and, Combined with HLA Class I, a Promising Prognostic Biomarker in Neuroblastoma

ARTICLE ABSTRACT

Purpose: This study sought to evaluate the expression of programmed cell death-ligand-1 (PD-L1) and HLA class I on neuroblastoma cells and programmed cell death-1 (PD-1) and lymphocyte activation gene 3 (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 IHC 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 IHC 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. Pharmacologic inhibition of MYCN and MYC may be exploited to target PD-L1 and restore an efficient antitumor immunity in high-risk neuroblastoma. Clin Cancer Res; 23(15); 4462–72. ©2017 AACR.