<p class="first" id="P3">Neuroblastoma is the most common pediatric solid tumor of
neural crest origin. The
current treatment options for neuroblastoma produce severe side effects. Programmed
death-ligand 1 (PD-L1), chronic inflammation, and non-coding RNAs are known to play
a significant role in the pathogenesis of neuroblastoma. Cancer cells and the surrounding
cells in the tumor microenvironment express PD-L1. Programmed death-1 (PD-1) is a
co-receptor expressed predominantly by T cells. The binding of PD-1 to its ligands,
PD-L1 or PD-L2, is vital for the physiologic regulation of the immune system. Chronic
inflammation is involved in the recruitment of leukocytes, production of cytokines
and chemokines that in turn, lead to survival, metastasis, and angiogenesis in neuroblastoma
tumors. The miRNAs and long non-coding (lnc) RNAs have emerged as a novel class of
non-coding RNAs that can regulate neuroblastoma associated cell-signaling pathways.
The dysregulation of PD-1/PD-L1, inflammatory pathways, lncRNAs, and miRNAs have been
reported in clinical and experimental samples of neuroblastoma. These signaling molecules
are currently being evaluated for their potential as the biomarker and therapeutic
targets in the management of neuroblastoma. A monoclonal antibody called dinutuximab
(Unituxin) that attaches to a carbohydrate molecule GD2, on the surface of many neuroblastoma
cells, is being used as an immunotherapy drug for neuroblastoma treatment. Atezolizumab
(Tecentriq), an engineered monoclonal antibody against PD-L1, are currently in clinical
trial for neuroblastoma patients. The lncRNA/miRNA-based therapeutics is being developed
to deliver tumor suppressor lncRNAs/miRNAs or silencing of oncogenic lncRNAs/miRNAs.
The focus of this review is to discuss the current knowledge on the immune checkpoint
molecules, PD-1/PD-L1 signaling, inflammation, and non-coding RNAs in neuroblastoma.
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