A Toolkit for Profiling the Immune Landscape of Pediatric Central Nervous System Malignancies
Rozowsky, Jacob S; Meesters-Ensing, Joyce I; Lammers, Julie A S; Belle, Muriël L; Nierkens, Stefan; Kranendonk, Mariëtte E G; Kester, Lennart A; Calkoen, Friso G; van der Lugt, Jasper
(2022) Frontiers in Immunology, volume 13, pp. 1 - 19
(Article)
Abstract
The prognosis of pediatric central nervous system (CNS) malignancies remains dismal due to limited treatment options, resulting in high mortality rates and long-term morbidities. Immunotherapies, including checkpoint inhibition, cancer vaccines, engineered T cell therapies, and oncolytic viruses, have promising results in some hematological and solid malignancies, and are being investigated
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in clinical trials for various high-grade CNS malignancies. However, the role of the tumor immune microenvironment (TIME) in CNS malignancies is mostly unknown for pediatric cases. In order to successfully implement immunotherapies and to eventually predict which patients would benefit from such treatments, in-depth characterization of the TIME at diagnosis and throughout treatment is essential. In this review, we provide an overview of techniques for immune profiling of CNS malignancies, and detail how they can be utilized for different tissue types and studies. These techniques include immunohistochemistry and flow cytometry for quantifying and phenotyping the infiltrating immune cells, bulk and single-cell transcriptomics for describing the implicated immunological pathways, as well as functional assays. Finally, we aim to describe the potential benefits of evaluating other compartments of the immune system implicated by cancer therapies, such as cerebrospinal fluid and blood, and how such liquid biopsies are informative when designing immune monitoring studies. Understanding and uniformly evaluating the TIME and immune landscape of pediatric CNS malignancies will be essential to eventually integrate immunotherapy into clinical practice.
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Keywords: central nervous system malignancy, flow cytometry, immune monitoring, immunohistochemistry, immunotherapy, transcriptomics, tumor immune microenvironment, Immunology and Allergy, Immunology
ISSN: 1664-3224
Publisher: Frontiers Media S. A.
Note: Funding Information: This study received funding from the Team Westland Foundation. JSR was supported by the Fulbright U.S. Student Grant and Netherland-American Foundation Pediatric Cancer Award. The funders were not involved in the study design, collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication. Publisher Copyright: Copyright © 2022 Rozowsky, Meesters-Ensing, Lammers, Belle, Nierkens, Kranendonk, Kester, Calkoen and van der Lugt.
(Peer reviewed)