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Updated: Dec 6, 2025

Three-Dimensional In Vitro Biomimetic Model of Neuroblastoma Using Collagen-Based Scaffolds
Published on: July 9, 2021
The Tumor Microenvironment in Neuroblastoma: New Players, New Mechanisms of Interaction and New Perspectives
Laurence Blavier1,2, Ren-Ming Yang1,2, Yves A DeClerck1,2,3
1The Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, CA 90027, USA.
Abstract:
The contribution of the tumor microenvironment (TME) to cancer progression has been well recognized in recent decades. As cancer therapeutic strategies are increasingly precise and include immunotherapies, knowledge of the nature and function of the TME in a tumor becomes essential. Our understanding of the TME in neuroblastoma (NB), the second most common solid tumor in children, has significantly progressed from an initial focus on its Schwannian component to a better awareness of its complex nature, which includes not only immune but also non-immune cells such as cancer-associated fibroblasts (CAFs), the contribution of which to inflammation and interaction with tumor-associated macrophages (TAMs) is now recognized. Recent studies on the TME landscape of NB tumors also suggest significant differences between MYCN-amplified (MYCN-A) and non-amplified (MYCN-NA) tumors, in their content in stromal and inflammatory cells and their immunosuppressive activity. Extracellular vesicles (EVs) released by cells in the TME and microRNAs (miRs) present in their cargo could play important roles in the communication between NB cells and the TME. This review article discusses these new aspects of the TME in NB and the impact that information on the TME landscape in NB will have in the design of precise, biomarker-integrated clinical trials.
Insights
The tumor microenvironment (TME) in neuroblastoma (NB) is complex, involving immune and non-immune cells. Understanding NB TME differences and extracellular vesicles (EVs) aids precise, biomarker-integrated cancer therapies.
Area of Science:
- Oncology
- Cancer Biology
- Immunology
Background:
- The tumor microenvironment (TME) significantly influences cancer progression and therapeutic responses.
- Neuroblastoma (NB), a common childhood cancer, has a complex TME involving immune cells, cancer-associated fibroblasts (CAFs), and tumor-associated macrophages (TAMs).
- Recent research highlights distinct TME landscapes in MYCN-amplified (MYCN-A) versus non-amplified (MYCN-NA) NB tumors, impacting immunosuppressive activity.
Purpose of the Study:
- To review current understanding of the neuroblastoma tumor microenvironment (TME).
- To discuss the role of cellular components and extracellular vesicles (EVs) in NB TME.
- To explore how TME insights can inform precise, biomarker-integrated clinical trials for NB.
Main Methods:
- Literature review of recent studies on neuroblastoma TME.
- Analysis of cellular and molecular components within the NB TME.
- Discussion of intercellular communication mechanisms, including EVs and microRNAs (miRs).
Main Results:
- The NB TME is more complex than previously thought, including non-immune cells like CAFs interacting with immune cells (TAMs).
- Significant differences exist in the TME composition and immunosuppressive activity between MYCN-A and MYCN-NA NB tumors.
- Extracellular vesicles (EVs) and their microRNA (miR) cargo are implicated in NB cell-TME communication.
Conclusions:
- A comprehensive understanding of the NB TME is crucial for developing advanced cancer therapies.
- TME characterization, including cellular and EV components, offers potential for targeted treatments.
- Future clinical trials for NB should integrate biomarker strategies informed by TME landscape analysis.

