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Immune contexture of paediatric cancers
Meghna Das Thakur1, Carl J Franz2, Laura Brennan3
1Genentech, South San Francisco, CA, USA.
European Journal of Cancer (Oxford, England : 1990)
|June 6, 2022
Summary
Paediatric solid tumours show a distinct immune microenvironment compared to adult cancers, with varying immune cell infiltration and antigen-presenting cell activity. Lower CD8 T-cell levels correlated with better prognosis in several paediatric cancers, suggesting new immunotherapy strategies.
Area of Science:
- Immunology
- Oncology
- Paediatric Medicine
Background:
- Immune checkpoint inhibitors have shown limited success in paediatric solid tumours.
- The immune microenvironment of paediatric malignancies is poorly understood compared to adult cancers.
Purpose of the Study:
- To investigate the immune microenvironment of five major paediatric cancers: Ewing sarcoma (ES), osteosarcoma (OS), rhabdomyosarcoma (RMS), medulloblastoma (MB), and neuroblastoma (NB).
- To correlate immune cell profiles with overall survival in these paediatric cancers.
- To understand the differences in immune contexture between paediatric and adult tumours.
Main Methods:
- Gene expression analysis and immunohistochemistry (IHC) were performed on 100 paediatric tumour samples (20 each of ES, OS, RMS, MB, NB).
- Immune cell populations, including T-cells, antigen-processing cells (APCs), macrophages, and regulatory T-cells (Tregs), were quantified.
- Tumour immune profiles were correlated with overall survival data.
Main Results:
- Neuroblastoma (NB) and rhabdomyosarcoma (RMS) showed high immune cell gene expression and T-cell counts, but low antigen-processing cell (APC) genes.
- Osteosarcoma (OS) and Ewing sarcoma (ES) had low T-cells but high APC genes; OS had high macrophages, while ES had low macrophages.
- Medulloblastoma (MB) presented as immune deserts. Tumour-infiltrating CD8 T-cell levels inversely correlated with prognosis in NB, RMS, and ES.
- MYCN-amplified NB had more immunosuppressive cells (macrophages, myeloid-derived suppressor cells, Tregs) compared to non-MYCN-amplified NB.
Conclusions:
- Paediatric cancers exhibit unique immune microenvironments distinct from adult tumours.
- The low efficacy of anti-PD(L)1 monotherapy in paediatric cancers may be attributed to these distinct immune profiles.
- Findings support the development of personalized, biologically stratified immunotherapies for children with relapsed or refractory cancers.
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