@article{9d5e72fb41f2406bae9329c452b66c65,
title = "Characterization of the Genomic and Immunologic Diversity of Malignant Brain Tumors through Multisector Analysis",
abstract = "Despite some success in secondary brain metastases, targeted or immune-based therapies have shown limited efficacy against primary brain malignancies such as glioblastoma (GBM). Although the intratumoral heterogeneity of GBM is implicated in treatment resistance, it remains unclear whether this diversity is observed within brain metastases and to what extent cancer cell–intrinsic heterogeneity sculpts the local immune microenvironment. Here, we profiled the immunogenomic state of 93 spatially distinct regions from 30 malignant brain tumors through wholeexome, RNA, and T-cell receptor sequencing. Our analyses identified differences between primary and secondary malignancies, with gliomas displaying more spatial heterogeneity at the genomic and neoantigen levels. In addition, this spatial diversity was recapitulated in the distribution of T-cell clones in which some gliomas harbored highly expanded but spatially restricted clonotypes. This study defines the immunogenomic landscape across a cohort of malignant brain tumors and contains implications for the design of targeted and immune-based therapies against intracranial malignancies.",
author = "Schaettler, {Maximilian O.} and Richters, {Megan M.} and Wang, {Anthony Z.} and Skidmore, {Zachary L.} and Bryan Fisk and Miller, {Katherine E.} and Vickery, {Tammi L.} and Kim, {Albert H.} and Chicoine, {Michael R.} and Osbun, {Joshua W.} and Leuthardt, {Eric C.} and Dowling, {Joshua L.} and Zipfel, {Gregory J.} and Dacey, {Ralph G.} and Lu, {Hsiang Chih} and Johanns, {Tanner M.} and Griffith, {Obi L.} and Mardis, {Elaine R.} and Malachi Griffith and Dunn, {Gavin P.}",
note = "Funding Information: Z.L. Skidmore reports grants from Washington University, St. Louis during the conduct of the study. A.H. Kim reports grants from Monteris Medical, Stryker, Collagen Matrix, and other support from Monteris Medical outside the submitted work. J.W. Osbun reports personal fees from Microvention, Inc., Medtronic, Inc., Terumo, Inc., and personal fees from InNeuroCo, Inc. outside the submitted work. E.C. Leuthardt reports personal fees and nonfinancial support from Monteris during the conduct of the study, other support from Neu-rolutions outside the submitted work, and stock ownership: Neuro-lutions, General Sensing, Osteovantage, Pear Therapeutics, Face to Face Biometrics, Immunovalent, Caeli Vascular, Acera, Sora Imaging Solutions, Inner Cosmos; consultant: Monteris Medical, E15, Acera, Alcyone, Intellectual Ventures, Medtronic, Inc., Neurolutions, Osteo-vantage, Pear Therapeutics, Inc., Sante Ventures, Microbot; SAB: Pear Therapeutics, Microbot; licensing from intellectual property: Neuro-lutions, Osteovantage, Caeli Vascular; licensing/product development agreements or royalties for inventions/IP: Cerovations, Intellectual Ventures. Washington University owns equity in Neurolutions. E.R. Mardis reports personal fees and other support from Qiagen N.V., personal fees and other support from PACT Pharma LLC, and personal fees and other support from Scorpion Therapeutics LLC outside the submitted work. G.P. Dunn reports personal fees from Ziopharm Oncology and personal fees from ImmunoGenesis outside the submitted work, and stock ownership from Immunovalent outside the submitted work. No disclosures were reported by the other authors. Publisher Copyright: {\textcopyright} 2021 The Authors; Published by the American Association for Cancer Research.",
year = "2022",
month = jan,
doi = "10.1158/2159-8290.CD-21-0291",
language = "English",
volume = "12",
pages = "154--171",
journal = "Cancer Discovery",
issn = "2159-8274",
number = "1",
}