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PD-1/PD-L1 blockade in paediatric cancers: What does the future hold?
Julia Moreno-Vicente1, Stephen A Beers1, Juliet C Gray1
1Antibody and Vaccine Group, Centre for Cancer Immunology, University of Southampton Faculty of Medicine, Department of Paediatric Oncology, Southampton, Hants, SO16 6YD, UK.
Insights
Checkpoint blockade (CPB) immunotherapy shows promise in adult cancers but faces challenges in children. Combinational therapies are crucial for improving CPB efficacy in paediatric malignancies.
Area of Science:
- Oncology
- Immunology
- Pediatrics
Background:
- Checkpoint blockade (CPB) immunotherapy is highly effective in adult cancers.
- Its application in paediatric oncology is limited, with disappointing response rates in early studies.
- Paediatric cancers present unique biological and immunological challenges for CPB translation.
Purpose of the Study:
- To provide an overview of CPB in paediatric cancers.
- To compare paediatric and adult cancer features impacting CPB success.
- To discuss strategies for optimizing CPB in children.
Main Methods:
- Review of pre-clinical and clinical experiences with CPB in paediatric populations.
- Analysis of unique biological and immunological aspects of paediatric cancers.
- Discussion of potential combinatorial therapeutic strategies.
Main Results:
- Paediatric cancers have distinct characteristics that influence CPB efficacy.
- Limited single-agent CPB studies in children show low response rates.
- Combinational approaches are likely necessary for therapeutic success.
Conclusions:
- Understanding paediatric cancer biology is key to successful CPB implementation.
- Combining CPB with chemotherapy, radiotherapy, or novel immunotherapies may enhance outcomes.
- Further research and clinical trials are needed to establish optimal CPB strategies for paediatric malignancies.
Abstract:
Checkpoint blockade (CPB) immunotherapy has shown unprecedented success in a wide range of adult malignancies, and is increasingly being employed in the treatment of advanced cancers. However, the experience in the paediatric population remains limited and the small number of single agent studies reported have shown disappointing response rates. Paediatric cancers offer unique challenges that can hinder the translation of CPB into the paediatric clinic, and combinational therapies are likely to be needed to achieve therapeutic success. As the number of paediatric trials using CPB rapidly increases, understanding the challenges that these agents may encounter in this population is of special significance to allow the design of optimal combinatorial strategies for each tumour type. Here, we offer an overview of the unique biological and immunological features of paediatric cancers as compared to adult malignancies, and how these might impact the overall success of CPB in the paediatric population. We review the growing body of pre-clinical and clinical experiences to date, and discuss future strategies involving the combination of CPB with traditionally used therapies (chemotherapy and radiotherapy) or with other newly developed immunotherapies.
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