Show simple item record

dc.contributor.authorLan, X.
dc.contributor.authorChu, C.
dc.contributor.authorJablonska, A.
dc.contributor.authorLiang, Y.
dc.contributor.authorJanowski, M.
dc.contributor.authorWalczak, P.
dc.date.accessioned2020-06-30T18:46:30Z
dc.date.available2020-06-30T18:46:30Z
dc.date.issued2020
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85086805327&doi=10.1080%2f2162402X.2020.1776577&partnerID=40&md5=db9b66b80b3bca9c1788033e1c720aa0
dc.identifier.urihttp://hdl.handle.net/10713/13200
dc.description.abstractCurrently, 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).en_US
dc.description.sponsorshipThis work was supported by the NIH/NINDS under Grant R01NS102675 and R01NS09111.en_US
dc.description.urihttps://doi.org/10.1080/2162402X.2020.1776577en_US
dc.language.isoen_USen_US
dc.publisherTaylor and Francis Inc.en_US
dc.relation.ispartofOncoImmunology
dc.subjectbrain tumoren_US
dc.subjectcostimulation blockadeen_US
dc.subjectGliomaen_US
dc.subjectimmunocompetenten_US
dc.subjecttoleranceen_US
dc.titleModeling human pediatric and adult gliomas in immunocompetent mice through costimulatory blockadeen_US
dc.typeArticleen_US
dc.identifier.doi10.1080/2162402X.2020.1776577


This item appears in the following Collection(s)

Show simple item record