Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020 Oct 10;12(10):2912.
doi: 10.3390/cancers12102912.

The Tumor Microenvironment in Neuroblastoma: New Players, New Mechanisms of Interaction and New Perspectives

Laurence Blavier  1   2 , Ren-Ming Yang  1   2 , Yves A DeClerck  1   2   3
Affiliations
Review

The Tumor Microenvironment in Neuroblastoma: New Players, New Mechanisms of Interaction and New Perspectives

Laurence Blavier et al. Cancers (Basel). .

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.

Keywords: MYCN; cancer-associated fibroblasts; extracellular vesicles; microRNA.; neuroblastoma; tumor microenvironment.

PubMed Disclaimer

Conflict of interest statement

The authors acknowledge no conflict of interest.

Figures

Figure 1
Figure 1
Contribution of MYCN to the TNME landscape in NB. Schematic representation of the TME landscape of a MYCN-A (cold) and a MYCN-NA (hot) tumor based on the review of the literature summarized in Table 1.
Figure 2
Figure 2
Considering the TME in the design of clinical trials in NB. Simplified conceptual design of a biomarker-integrated umbrella protocol in NB based on genomic and TME information.
See this image and copyright information in PMC

References

    1. Borriello L., Seeger R.C., Asgharzadeh S., Declerck Y.A. More than the genes, the tumor microenvironment in neuroblastoma. Cancer Lett. 2016;380:304–314. doi: 10.1016/j.canlet.2015.11.017. - DOI - PMC - PubMed
    1. Taxy J.B. Electron microscopy in the diagnosis of neuroblastoma. Arch. Pathol. Lab. Med. 1980;104:355–360. - PubMed
    1. Shimada H., Ambros I.M., Dehner L.P., Hata J., Joshi V.V., Roald B., Stram D.O., Gerbing R.B., Lukens J.N., Matthay K.K., et al. The international neuroblastoma pathology classification (the Shimada system) Cancer. 1999;86:364–372. doi: 10.1002/(SICI)1097-0142(19990715)86:2<364::AID-CNCR21>3.0.CO;2-7. - DOI - PubMed
    1. Rössler J., Breit S., Havers W., Schweigerer L. Vascular endothelial growth factor expression in human neuroblastoma: Up-regulation by hypoxia. Int. J. Cancer. 1999;81:113–117. doi: 10.1002/(SICI)1097-0215(19990331)81:1<113::AID-IJC19>3.0.CO;2-L. - DOI - PubMed
    1. Zeine R., Salwen H.R., Peddinti R., Tian Y., Guerrero L., Yang Q., Chlenski A., Cohn S.L. Presence of cancer-associated fibroblasts inversely correlates with Schwannian stroma in neuroblastoma tumors. Mod. Pathol. 2009;22:950–958. doi: 10.1038/modpathol.2009.52. - DOI - PMC - PubMed