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Updated: May 28, 2026
Predictive Immune Modeling of Solid Tumors
Published on: February 25, 2020
Distinct signatures of the immune responses in low risk versus high risk neuroblastoma
Madhu Gowda1, Kamar Godder, Maciej Kmieciak
1Department of Pediatrics, Children's Hospital of Richmond, Richmond, VA, USA. MSGowda@mcvh-vcu.edu
Insights
High-risk neuroblastoma shows active T-cell responses, suggesting adaptive immunity drives progression. Low-risk neuroblastoma exhibits diminished adaptive immunity but intact innate immune responses, aiding survival.
Area of Science:
- Immunology
- Oncology
- Pediatric Cancer Research
Background:
- Neuroblastoma risk stratification significantly impacts patient survival rates.
- Age is a key factor, with younger children (<18 months) typically having low-risk disease.
- Adaptive immunity, particularly T-cell responses, is crucial in cancer progression and immune escape.
Purpose of the Study:
- To investigate differences in immune responses between high-risk (HR) and low-risk (LR) neuroblastoma patients.
- To determine if HR patients exhibit adaptive immune signatures, while LR patients show diminished T-cell and intact innate responses.
Main Methods:
- Microarray analysis of tumor RNA from HR and LR patients.
- Flow cytometry for blood cell analysis and multiplex cytokine arrays for serum profiling.
- In vitro study of a HR tumor cell line's response to IL-1β.
Main Results:
- Distinct gene expression patterns revealed active T-cell responses in HR and diminished adaptive immunity in LR patients.
- LR patients had higher IL-10 levels, indicating a weaker adaptive immune response.
- HR patients showed lower myeloid-derived suppressor cells (MDSC), while LR patients had higher innate immune cytokines.
Conclusions:
- Adaptive immune responses appear critical in high-risk neuroblastoma progression.
- Innate immune responses may be more active in low-risk neuroblastoma patients.
Background:
Over 90% of low risk (LR) neuroblastoma patients survive whereas less than 30% of high risk (HR) patients are long term survivors. Age (children younger than 18 months old) is associated with LR disease. Considering that adaptive immune system is well developed in older children, and that T cells were shown to be involved in tumor escape and progression of cancers, we sought to determine whether HR patients may tend to show a signature of adaptive immune responses compared to LR patients who tend to have diminished T-cell responses but an intact innate immune response.
Methods:
We performed microarray analysis of RNA extracted from the tumor specimens of HR and LR patients. Flow cytometry was performed to determine the cellular constituents in the blood while multiplex cytokine array was used to detect the cytokine profile in patients' sera. A HR tumor cell line, SK-N-SH, was also used for detecting the response to IL-1β, a cytokines which is involved in the innate immune responses.
Results:
Distinct patterns of gene expression were detected in HR and LR patients indicating an active T-cell response and a diminished adaptive immune response, respectively. A diminished adaptive immune response in LR patients was evident by higher levels of IL-10 in the sera. In addition, HR patients had lower levels of circulating myeloid derived suppressor cells (MDSC) compared with a control LR patient. LR patients showed slightly higher levels of cytokines of the innate immune responses. Treatment of the HR tumor line with IL-1β induced expression of cytokines of the innate immune responses.
Conclusions:
This data suggests that adaptive immune responses may play an important role in the progression of HR disease whereas innate immune responses may be active in LR patients.