Cancer Chemotherapy and Pharmacology

, Volume 80, Issue 6, pp 1047–1053 | Cite as

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

  • Maurizio Lucchesi
  • Iacopo Sardi
  • Gianfranco Puppo
  • Antonio Chella
  • Claudio Favre
Review Article
Part of the following topical collections:
  1. Cytotoxic Reviews


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.


Checkpoint inhibitors Immunotherapy Pediatric solid tumors CTLA-4 PD-1 PD-L1 



Cytotoxic T lymphocyte antigen 4


Programmed cell death protein 1


PD-1 ligand 1


Lung cancer


Renal clear cell carcinoma


Hodgkin’s lymphoma


Immune-related adverse events


Hematologic stem cell transplantation


Graft-versus-host disease


Biallelic mismatch repair deficiency


Central nervous system


Compliance with ethical standards


No funding.

Conflict of interest

All authors have no conflicts of interest.

Ethical approval

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


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Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Maurizio Lucchesi
    • 1
    • 4
  • Iacopo Sardi
    • 2
    • 3
    • 4
  • Gianfranco Puppo
    • 1
  • Antonio Chella
    • 1
    • 4
  • Claudio Favre
    • 3
    • 4
  1. 1.Pulmonology Unit, Thoracic Cancer CenterAzienda Ospedaliero-Universitaria PisanaPisaItaly
  2. 2.Neuro-Oncology UnitAnna Meyer Children’s HospitalFlorenceItaly
  3. 3.Department of Pediatric Oncology, Hematology, and TransplantsAnna Meyer Children’s HospitalFlorenceItaly
  4. 4.Tuscany Network for Paediatric Oncology-Istituto Toscano Tumori (ITT)FlorenceItaly

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