Abstract
Neuroblastoma (NBL) is the most common extracranial solid tumor in childhood. Despite intense treatment, children with this high-risk disease have a poor prognosis. Immunotherapy showed a significant improvement in event-free survival in high-risk NBL patients receiving chimeric anti-GD2 in combination with cytokines and isotretinoin after myeloablative consolidation therapy. However, response to immunotherapy varies widely, and often therapy is stopped due to severe toxicities. Objective markers that help to predict which patients will respond or develop toxicity to a certain treatment are lacking. Immunotherapy guided via immune monitoring protocols will help to identify responders as early as possible, to decipher the immune response at play, and to adjust or develop new treatment strategies. In this review, we summarize recent studies investigating frequency and phenotype of immune cells in NBL patients prior and during current treatment protocols and highlight how these findings are related to clinical outcome. In addition, we discuss potential targets to improve immunogenicity and strategies that may help to improve therapy efficacy. We conclude that immune monitoring during therapy of NBL patients is essential to identify predictive biomarkers to guide patients towards effective treatment, with limited toxicities and optimal quality of life.
Highlights
Neuroblastoma (NBL) is a tumor derived from sympathoadrenal progenitor cells of the developing sympathetic nervous system
Administration of the chimeric monoclonal antibody anti-GD2, combined with the cytokines IL-2 and granulocyte macrophage-colony stimulation factor (GM-CSF), and isotretinoin in patients with high-risk NBL resulted in a significant increase 2-year event-free (EFS) and overall survival (OS) [10]
This review provides an overview of predictive immune biomarkers of clinical response to treatment, emphasizes the importance of immune monitoring during NBL treatment, and describes its relevance for evaluation of the immune response and patient stratification by developing new biomarkers
Summary
Neuroblastoma (NBL) is a tumor derived from sympathoadrenal progenitor cells of the developing sympathetic nervous system. Administration of the chimeric monoclonal antibody (mAb) anti-GD2 (ch14.18), combined with the cytokines IL-2 and granulocyte macrophage-colony stimulation factor (GM-CSF), and isotretinoin in patients with high-risk NBL resulted in a significant increase 2-year event-free (EFS) and overall survival (OS) [10] The observation of this effect, despite the harsh immunomodulatory immune environment of NBL, shows the potential of immune interference in NBL. Mina et al showed that the prognostic value of TIL levels at diagnosis is even better than criteria currently used to stage NBL, such as MYCN amplification [8] This illustrates the potential role of immune cells in influencing the clinical outcome and emphasizes the need for standardized immune monitoring during therapy in this patient group. This review provides an overview of predictive immune biomarkers of clinical response to treatment, emphasizes the importance of immune monitoring during NBL treatment, and describes its relevance for evaluation of the immune response and patient stratification by developing new biomarkers
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