East Montgomery Times

Researchers at the Children's Hospital of Philadelphia (CHOP) have developed a comprehensive cell atlas of neuroblastoma, aiming to shed light on the tumor's microenvironment, which plays a critical role in treatment efficacy. The results, promising advancements in personalized medicine approaches for this childhood cancer, have been published in the journal Nature Genetics.

Despite oncological progress, the 5-year survival rate for high-risk neuroblastoma remains below 50%. The variability within tumor cells creates significant treatment challenges. Researchers at CHOP have created a cell atlas offering a detailed view of how different cell types within the tumor interact and change throughout treatment, addressing a gap in existing scientific knowledge.

"Our atlas provides a crucial foundation for developing novel treatments by mapping the complex interactions between malignant cells and surrounding cells that support tumor growth," said Kai Tan, PhD. Tan is a professor in the Department of Pediatrics at CHOP and heads the hospital's involvement in the National Cancer Institute (NCI) Human Tumor Atlas Network (HTAN). "As researchers, we look to use these insights to tailor therapies to target unique characteristics of a patient’s tumor. Overall, we are optimistic about the doors our research and techniques are opening."

The study utilized advanced single-cell sequencing and spatial omics techniques to examine tumor samples from 22 pediatric patients with high-risk neuroblastoma, both before and after chemotherapy. This data is available on the HTAN data portal.

The research revealed that rapid multiplication and increased metabolic activity of cancer cells correlate with poorer outcomes, whereas tumors exhibiting mature, neuron-like features correlate with better prognoses. Moreover, an uptick in mesenchymal-like tumor cells was connected to reduced chemotherapy efficacy. Macrophages showed increased activity that supported tumor growth by facilitating blood vessel formation while dampening immune response.

A specific signaling pathway between macrophages and cancer calls (HB-EGF/ERBB4) was identified, which promotes tumor growth. The findings emphasize the importance of understanding the tumor microenvironment to improve responses to treatment. Preclinical models are being used to further explore this pathway with hopes of developing new treatment strategies.

"Studies of this magnitude are only made possible by monumental team efforts," said Wenbao Yu, PhD, a lead author of the study and a Research Assistant Professor at CHOP. "With the collaboration of biologists, clinicians, and computational scientists, we were able to gain new insights into the complex ecosystem of neuroblastoma."

The research received backing from the National Cancer Institute (NCI) Human Tumor Atlas Network grant (#U2C CA233285), along with support from a National Institutes of Health (NIH) grant (U54 HL165442), an American Cancer Society Institutional Research Grant (IRG-22-150-41-IRG), and another NIH grant (T32 CA009140).

Yu et al. "Longitudinal single-cell multiomic atlas of high-risk neuroblastoma reveals chemotherapy-induced tumor microenvironment rewiring. Nature Genetics. Online April 14, 2025. DOI: 10.1038/s41588-025-02158-6.