Lineage-dependence of the neuroblastoma surfaceome defines tumor cell state-dependent and independent immunotherapeutic targets.

Background: Neuroblastoma is a heterogeneous disease with adrenergic (ADRN)- and therapy resistant mesenchymal (MES)-like cells driven by distinct transcription factor networks. Here, we investigate the expression of immunotherapeutic targets in each neuroblastoma subtype and propose pan-neuroblastoma and cell state specific targetable cell-surface proteins.

Methods: We characterized cell lines, patient-derived xenografts, and patient samples as ADRN-dominant or MES-dominant to define subtype-specific and pan-neuroblastoma gene sets.

Identification and Characterization of Chemotherapy-Resistant High-Risk Neuroblastoma Persister Cells.

Relapse rates in high-risk neuroblastoma remain exceedingly high. The malignant cells that are responsible for relapse have not been identified, and mechanisms of therapy resistance remain poorly understood. In this study, we used single-nucleus RNA sequencing and bulk whole-genome sequencing to identify and characterize the residual malignant persister cells that survive chemotherapy from a cohort of 20 matched diagnosis and definitive surgery tumor samples from patients treated with high-risk neuroblastoma induction chemotherapy.

BPTF cooperates with MYCN and MYC to link neuroblastoma cell cycle control to epigenetic cellular states.

The nucleosome remodeling factor BPTF is required for the deployment of the MYC-driven transcriptional program. Deletion of one allele delays tumor progression in mouse models of pancreatic cancer and lymphoma. In neuroblastoma, MYCN cooperates with the transcriptional core regulatory circuitry (CRC).

Epigenetic state determines inflammatory sensing in neuroblastoma.

Immunotherapy has revolutionized cancer treatment, but many cancers are not impacted by currently available immunotherapeutic strategies. Here, we investigated inflammatory signaling pathways in neuroblastoma, a classically "cold" pediatric cancer. By testing the functional response of a panel of 20 diverse neuroblastoma cell lines to three different inflammatory stimuli, we found that all cell lines have intact interferon signaling, and all but one lack functional cytosolic DNA sensing via cGAS-STING.

Refining immunotherapeutic approaches to high-risk neuroblastoma based on tumor genomic profiles.

In this issue, Coronado et al. attempt to improve our understanding of the factors affecting the response to immunotherapy in a large subset of high-risk neuroblastoma with hemizygous deletion of chromosome 11q. By using several computational approaches, the authors study potential transcriptional and post-transcriptional pathways that may affect the response to immunotherapy and further be leveraged therapeutically in a biomarker-directed fashion.

Multiple bloodstream infections in pediatric stem cell transplant recipients: A case series.

Bacterial bloodstream infections (BSIs) are associated with poor outcomes following stem cell transplantation (SCT). We describe the demographics, treatment, complications, and outcome of 23 pediatric SCT recipients who developed three or more BSIs in the first year after SCT at our center from 2011 through 2016. The majority underwent allogeneic SCT (n = 22/23;96%), mainly from an unrelated donor (n = 19/22,86%); developed grade 2-4 graft versus host disease (GVHD; n = 14/23, 61%), all steroid refractory; and were diagnosed with thrombotic microangiopathy (n = 21/23, 91%).

Egg Food Challenges are Associated with More Gastrointestinal Reactions.

Egg allergy is a common pediatric allergy, and is usually outgrown by elementary school age. There is, therefore, a need to perform an oral food challenge (OFC) to establish the presence of food allergy to egg. In this study, we conducted a retrospective review of 2304 OFCs at a pediatric center and analyzed the severity of reactions during egg OFCs and compared them with other foods.