A Toolkit for Profiling the Immune Landscape of Pediatric Central Nervous System Malignancies

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, ha...

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Bibliographic Details
Published in:	Frontiers in immunology Vol. 13; p. 864423
Main Authors:	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
Format:	Journal Article
Language:	English
Published:	Switzerland Frontiers Media S.A 07-04-2022
Subjects:	Cancer Vaccines - therapeutic use central nervous system malignancy Central Nervous System Neoplasms - therapy Child flow cytometry Humans immune monitoring immunohistochemistry Immunology immunotherapy Immunotherapy - methods Oncolytic Viruses tumor immune microenvironment Tumor Microenvironment central nervous system malignancy tumor immune microenvironment immunotherapy transcriptomics flow cytometry immune monitoring immunohistochemistry
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Summary:	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 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 ObjectType-Review-3 content type line 23 These authors have contributed equally to this work Edited by: Orazio Vittorio, University of New South Wales, Australia Reviewed by: Jiyang Yu, St. Jude Children’s Research Hospital, United States; Raelene Endersby, University of Western Australia, Australia This article was submitted to Cancer Immunity and Immunotherapy, a section of the journal Frontiers in Immunology
ISSN:	1664-3224 1664-3224
DOI:	10.3389/fimmu.2022.864423