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Landi et al. Neuroimmunol Neuroinflammation 2018;5:29 Neuroimmunology and
DOI: 10.20517/2347-8659.2018.35 Neuroinflammation

Review Open Access

Immunotherapy for pediatric brain tumors

Daniel B. Landi , Eric M. Thompson 1,2,3 , David M. Ashley 1,2,3
1,2
1 Preston Robert Tisch Brain Tumor Center, Durham, NC 27710, USA.
2 Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA.
3 Department of Neurosurgery, Duke University Medical Center, Durham, NC 27710, USA.

Correspondence to: Dr. Daniel B. Landi, Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA.
E-mail: daniel.landi@duke.edu

How to cite this article: Landi DB, Thompson EM, Ashley DM. Immunotherapy for pediatric brain tumors. Neuroimmunol
Neuroinflammation 2018;5:29. http://dx.doi.org/10.20517/2347-8659.2018.35
Received: 8 Jun 2018 First Decision: 2 Jul 2018 Revised: 13 Jul 2018 Accepted: 16 Jul 2018 Published: 23 Jul 2018

Science Editor: Athanassios P. Kyritsis Copy Editor: Jun-Yao Li Production Editor: Huan-Liang Wu

ABSTRACT
Immunotherapy, while effective against lymphoid cancers and some solid tumors, has shown less benefit against
pediatric brain tumors. Tumor heterogeneity, a suppressive immune microenvironment, and the blood-brain barrier
have the potential to diminish any immune-based approach and limit efficacy. More importantly, most pediatric
brain tumors are immunologically quiescent, stemming from a low mutational burden. This review focuses on innate
vs. adaptive immunotherapeutic approaches and describes how the immunologic context of pediatric brain tumors
can help identify well-suited immunotherapies for our patients. In this framework, we will discuss past and current
approaches using virotherapy, immunoconjugates, monoclonal antibodies, active immunization, and adoptive cel-
lular therapy, and share our thoughts on how immunotherapy can cure children with brain tumors.

Keywords: Immunotherapy, brain tumor, pediatrics, virotherapy, active immunization, adoptive cellular therapy

INTRODUCTION
The incidence of pediatric brain tumors varies by country and ranges between 1-5 cases/100,000 persons,
[1,2]
with about 4600 primary central nervous system tumors diagnosed in the United States annually . There
are over 100 histologic subtypes of brain tumors, but the most common diagnoses in children are low-grade
gliomas, particularly pilocytic astrocytoma (incidence roughly 0.8/100,000) and medulloblastoma (incidence
[2]
roughly 0.4/100,000) . Outcomes for recurrent malignant brain tumors in children remain poor, and brain
[3]
tumors are the leading cause of cancer death in children . Even when effective, surgery, radiation, and che-
motherapy cause neurologic and neurocognitive morbidity. Many children with brain tumors who survive
© The Author(s) 2018. Open Access This article is licensed under a Creative Commons Attribution 4.0
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