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Updated: Jun 16, 2026
Differentiation of the SH-SY5Y Human Neuroblastoma Cell Line
Published on: February 17, 2016
Single-cell transcriptomics reveals shared immunosuppressive landscapes of mouse and human neuroblastoma
Ana Costa1,2, Cécile Thirant1,2, Amira Kramdi1,2
1Inserm U830, Equipe Labellisée LNCC, Diversity and Plasticity of Childhood Tumors Lab, PSL Research University, Institut Curie Research Centre, Paris, France.
Background:
High-risk neuroblastoma is a pediatric cancer with still a dismal prognosis, despite multimodal and intensive therapies. Tumor microenvironment represents a key component of the tumor ecosystem the complexity of which has to be accurately understood to define selective targeting opportunities, including immune-based therapies.
Methods:
We combined various approaches including single-cell transcriptomics to dissect the tumor microenvironment of both a transgenic mouse neuroblastoma model and a cohort of 10 biopsies from neuroblastoma patients, either at diagnosis or at relapse. Features of related cells were validated by multicolor flow cytometry and functional assays.
Results:
We show that the immune microenvironment of MYCN-driven mouse neuroblastoma is characterized by a low content of T cells, several phenotypes of macrophages and a population of cells expressing signatures of myeloid-derived suppressor cells (MDSCs) that are molecularly distinct from the various macrophage subsets. We document two cancer-associated fibroblasts (CAFs) subsets, one of which corresponding to CAF-S1, known to have immunosuppressive functions. Our data unravel a complex content in myeloid cells in patient tumors and further document a striking correspondence of the microenvironment populations between both mouse and human tumors. We show that mouse intratumor T cells exhibit increased expression of inhibitory receptors at the protein level. Consistently, T cells from patients are characterized by features of exhaustion, expressing inhibitory receptors and showing low expression of effector cytokines. We further functionally demonstrate that MDSCs isolated from mouse neuroblastoma have immunosuppressive properties, impairing the proliferation of T lymphocytes.
Conclusions:
Our study demonstrates that neuroblastoma tumors have an immunocompromised microenvironment characterized by dysfunctional T cells and accumulation of immunosuppressive cells. Our work provides a new and precious data resource to better understand the neuroblastoma ecosystem and suggest novel therapeutic strategies, targeting both tumor cells and components of the microenvironment.
Insights
Neuroblastoma tumors feature an immunocompromised microenvironment with dysfunctional T cells and immunosuppressive myeloid-derived suppressor cells (MDSCs). This finding offers new therapeutic targets for this pediatric cancer.
Area of Science:
- Pediatric Oncology
- Cancer Immunology
- Tumor Microenvironment Research
Background:
- High-risk neuroblastoma has a poor prognosis despite intensive therapies.
- Understanding the tumor microenvironment is crucial for developing targeted therapies, including immunotherapies.
Purpose of the Study:
- To dissect the tumor microenvironment in a mouse model and human neuroblastoma patient samples.
- To identify cellular components and their functional roles within the neuroblastoma ecosystem.
Main Methods:
- Single-cell transcriptomics was employed on a mouse neuroblastoma model and 10 patient biopsies.
- Multicolor flow cytometry and functional assays were used for validation.
- Analysis included characterization of immune cells and cancer-associated fibroblasts.
Main Results:
- Neuroblastoma exhibits a T cell-poor immune microenvironment with diverse macrophage populations and distinct myeloid-derived suppressor cells (MDSCs).
- Two cancer-associated fibroblast (CAF) subsets were identified, including immunosuppressive CAF-S1.
- Mouse and human tumors showed conserved microenvironment populations, with T cells displaying exhaustion markers and MDSCs demonstrating immunosuppressive function.
Conclusions:
- Neuroblastoma tumors possess an immunocompromised microenvironment with dysfunctional T cells and immunosuppressive cells.
- This research provides valuable data for understanding the neuroblastoma ecosystem.
- Novel therapeutic strategies targeting tumor cells and microenvironment components are suggested.
