Checkpoint proteins in pediatric brain and extracranial solid tumors: Opportunities for immunotherapy

Eric K. Ring, James M. Markert, G. Yancey Gillespie, Gregory K. Friedman

Research output: Contribution to journalReview article

16 Citations (Scopus)

Abstract

Pediatric brain and extracranial solid tumors are a diverse group of malignancies that represent almost half of all pediatric cancers. Standard therapy includes various combinations of surgery, cytotoxic chemotherapy, and radiation, which can be very harmful to a developing child, and survivors carry a substantial burden of longterm morbidities. Although these therapies have improved survival rates for children with solid tumors, outcomes still remain extremely poor for subsets of patients. Recently, immunosuppressive checkpoint molecules that negatively regulate immune cell function have been described. When found on malignant cells or in the tumor microenvironment, they contribute to immune evasion and tumor escape. Agents designed to inhibit these proteins have demonstrated significant efficacy in human adult solid tumor studies. However, there is limited research focusing on immune checkpoint molecules and inhibitors in pediatric solid tumors. In this review, we examine the current knowledge on immune checkpoint proteins with an emphasis on cytotoxic T lymphocyte antigen-4 (CTLA-4); programmed cell death protein- 1 (PD-1) and programmed death-ligand 1 (PD-L1); OX-2 membrane glycoprotein (CD200); and indoleamine 2,3-dioxygenase (IDO). We review T-cell signaling, the mechanisms of action of these checkpoint molecules, pediatric preclinical studies on checkpoint proteins and checkpoint blockade, pediatric checkpoint inhibitor clinical trials conducted to date, and future immunotherapy opportunities for childhood cancers.

Original languageEnglish (US)
Pages (from-to)342-350
Number of pages9
JournalClinical Cancer Research
Volume23
Issue number2
DOIs
StatePublished - Jan 15 2017

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Immunotherapy
Pediatrics
Brain
Neoplasms
Proteins
Programmed Cell Death 1 Receptor
CTLA-4 Antigen
Indoleamine-Pyrrole 2,3,-Dioxygenase
Tumor Escape
Immune Evasion
Tumor Microenvironment
Immunosuppressive Agents
Survivors
Survival Rate
Clinical Trials
Radiation
Ligands
Morbidity
T-Lymphocytes
Drug Therapy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Checkpoint proteins in pediatric brain and extracranial solid tumors : Opportunities for immunotherapy. / Ring, Eric K.; Markert, James M.; Gillespie, G. Yancey; Friedman, Gregory K.

In: Clinical Cancer Research, Vol. 23, No. 2, 15.01.2017, p. 342-350.

Research output: Contribution to journalReview article

Ring, Eric K. ; Markert, James M. ; Gillespie, G. Yancey ; Friedman, Gregory K. / Checkpoint proteins in pediatric brain and extracranial solid tumors : Opportunities for immunotherapy. In: Clinical Cancer Research. 2017 ; Vol. 23, No. 2. pp. 342-350.
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