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The dawn of “immune-revolution” in children: early experiences with checkpoint inhibitors in childhood malignancies

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Abstract

Modern immunotherapy with checkpoint inhibitors has changed clinical practice of adult patients with advanced cancer. Blockade of CTLA-4 and PD-1 pathways have shown survival benefits in different diseases. In children, combination of surgery, radiotherapy and chemotherapy have improved survival rates of solid tumors. However, the outcomes for subsets of patients such as those with high-grade, refractory, or metastatic disease remain extremely poor. Currently, the treatment of these patients is almost exclusively based on standard chemotherapy. The significant proportion of pediatric cancers with high number of mutations and subsequent high expression of neoantigens, together with the potential prognostic role of the immunosuppressive checkpoint molecules (CTLA-4, PD-L1) can represent a promising rationale that support the use of checkpoint inhibitors. We made a revision about emerging data regarding safety and activity of checkpoint inhibitors in children with solid tumors.

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Abbreviations

CTLA4:

Cytotoxic T lymphocyte antigen 4

PD1:

Programmed cell death protein 1

PD-L1:

PD-1 ligand 1

NSCLC:

Lung cancer

RCC:

Renal clear cell carcinoma

HL:

Hodgkin’s lymphoma

irAE:

Immune-related adverse events

HSCT:

Hematologic stem cell transplantation

GVHD:

Graft-versus-host disease

bMMRD:

Biallelic mismatch repair deficiency

CNS:

Central nervous system

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Correspondence to Maurizio Lucchesi.

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All authors have no conflicts of interest.

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This article does not contain any studies with human participants performed by any of the authors.

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Lucchesi, M., Sardi, I., Puppo, G. et al. The dawn of “immune-revolution” in children: early experiences with checkpoint inhibitors in childhood malignancies. Cancer Chemother Pharmacol 80, 1047–1053 (2017). https://doi.org/10.1007/s00280-017-3450-2

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