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    Modeling human pediatric and adult gliomas in immunocompetent mice through costimulatory blockade

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    Author
    Lan, X.
    Chu, C.
    Jablonska, A.
    Liang, Y.
    Janowski, M.
    Walczak, P.
    Date
    2020
    Journal
    OncoImmunology
    Publisher
    Taylor and Francis Inc.
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://doi.org/10.1080/2162402X.2020.1776577
    Abstract
    Currently, human glioma tumors are mostly modeled in immunodeficient recipients; however, lack of interactions with adaptive immune system is a serious flaw, particularly in the era when immunotherapies dominate treatment strategies. Our group was the first to successfully establish the orthotopic transplantation of human glioblastoma (GBM) in immunocompetent mice by inducing immunological tolerance using a short-term, systemic costimulation blockade strategy (CTLA-4-Ig and MR1). In this study, we further validated the feasibility of this method by modeling pediatric diffuse intrinsic pontine glioma (DIPG) and two types of adult GBM (GBM1, GBM551), in mice with intact immune systems and immunodeficient mice. We found that all three glioma models were successfully established, with distinct difference in tumor growth patterns and morphologies, after orthotopic xenotransplantation in tolerance-induced immunocompetent mice. Long-lasting tolerance that is maintained for up to nearly 200 d in GBM551 confirmed the robustness of this model. Moreover, we found that tumors in immunocompetent mice displayed features more similar to the clinical pathophysiology found in glioma patients, characterized by inflammatory infiltration and strong neovascularization, as compared with tumors in immunodeficient mice. In summary, we have validated the robustness of the costimulatory blockade strategy for tumor modeling and successfully established three human glioma models including the pediatric DIPG whose preclinical study is particularly thwarted by the lack of proper animal models. Copyright 2020 the Author(s).
    Sponsors
    This work was supported by the NIH/NINDS under Grant R01NS102675 and R01NS09111.
    Keyword
    brain tumor
    costimulation blockade
    Glioma
    immunocompetent
    tolerance
    Identifier to cite or link to this item
    https://www.scopus.com/inward/record.uri?eid=2-s2.0-85086805327&doi=10.1080%2f2162402X.2020.1776577&partnerID=40&md5=db9b66b80b3bca9c1788033e1c720aa0; http://hdl.handle.net/10713/13200
    ae974a485f413a2113503eed53cd6c53
    10.1080/2162402X.2020.1776577
    Scopus Count
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    UMB Open Access Articles 2020

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