Targeting Neuroinflammation in Brain Cancer: Uncovering Mechanisms, Pharmacological Targets, and Neuropharmaceutical Developments.
Mahmoud S. Alghamri,Brandon L. McClellan,Margaret S. Hartlage,Santiago Haase,Syed M Faisal,Rohit Thalla,Ali Dabaja,Kaushik Banerjee,Stephen Carney,Anzar A. Mujeeb,Michael R. Olin,James J. Moon,Anna Schwendeman,Pedro R. Lowenstein,Maria G. Castro +14 more
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TLDR
Glioblastomas are one of the most lethal types of cancers accounting for ~80% of all central nervous system (CNS) primary malignancies [1, as discussed by the authors.Abstract:
Gliomas are one of the most lethal types of cancers accounting for ~80% of all central nervous system (CNS) primary malignancies [1; 2]. Amongst gliomas, glioblastomas (GBM) are the most aggressive, characterized by a median patient survival of fewer than 15 months. Recent molecular characterization studies uncovered the genetic signatures and methylation status of gliomas and correlate these with clinical prognosis [2]. The most relevant molecular characteristics for the new glioma classification are IDH mutation, chromosome 1p/19q deletion, histone mutations, and other genetic parameters such as ATRX loss, TP53, and TERT mutations, as well as DNA methylation levels. Similar to other solid tumors, glioma progression is impacted by the complex interactions between the tumor cells and immune cells within the tumor microenvironment. The immune system’s response to cancer can impact the glioma’s survival, proliferation, and invasiveness. Salient characteristics of gliomas include enhanced vascularization, stimulation of a hypoxic tumor microenvironment, increased oxidative stress, and an immune suppressive milieu. These processes promote the neuro-inflammatory tumor microenvironment which can lead to the loss of blood-brain barrier (BBB) integrity. The consequences of a compromised BBB are deleteriously exposing the brain to potentially harmful concentrations of substances from the peripheral circulation, adversely affecting neuronal signaling, and abnormal immune cell infiltration; all of which can lead to disruption of brain homeostasis. In this review, we first describe the unique features of inflammation in CNS tumors. We then discuss the mechanisms of tumor-initiating neuro-inflammatory microenvironment and its impact on tumor invasion and progression. Finally, we also discuss potential pharmacological interventions that can be used to target neuro-inflammation in gliomas.read more
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RNA binding by ADAR3 inhibits adenosine-to-inosine editing and promotes expression of immune response protein MAVS
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References
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Derek A. Wainwright,Irina V. Balyasnikova,Alan L. Chang,Atique U. Ahmed,Kyung Sub Moon,Brenda Auffinger,Alex Tobias,Yu Han,Maciej S. Lesniak +8 more
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Combination therapy with anti-PD-1, anti-TIM-3, and focal radiation results in regression of murine gliomas
Jennifer E. Kim,Mira A. Patel,Antonella Mangraviti,Eileen S. Kim,Debebe Theodros,Esteban Velarde,Ann Liu,Eric W. Sankey,Ada Tam,Haiying Xu,Dimitrios Mathios,Christopher M. Jackson,Sarah Harris-Bookman,Tomas Garzon-Muvdi,Mary Sheu,Allison Martin,Betty Tyler,Phuoc T. Tran,Xiaobu Ye,Alessandro Olivi,Janis M. Taube,Peter C. Burger,Charles G. Drake,Henry Brem,Drew M. Pardoll,Michael Lim +25 more
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Gliomas induce and exploit microglial MT1-MMP expression for tumor expansion.
Darko Markovic,Katyayni Vinnakota,Sridhar Reddy Chirasani,Michael Synowitz,H. Raguet,Kristin Stock,Marcin Sliwa,S.C. Lehmann,Roland E. Kälin,N. van Rooijen,Kenn Holmbeck,Frank L. Heppner,Jürgen C. W. Kiwit,Vitali Matyash,Seija Lehnardt,Bozena Kaminska,Rainer Glass,Helmut Kettenmann +17 more
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Toll-like receptors activate innate and adaptive immunity by using dendritic cell-intrinsic and -extrinsic mechanisms.
TL;DR: The generation of mice selectively lacking the crucial TLR-signaling adaptor MyD88 in dendritic cells is reported, demonstrating that DCs and other innate immune cells can respond via TLRs and collaborate in promoting Th1 adaptive immune responses to an aggregated stimulus.
Journal ArticleDOI
HMGB1 Mediates Endogenous TLR2 Activation and Brain Tumor Regression
James F. Curtin,James F. Curtin,Naiyou Liu,Naiyou Liu,Marianela Candolfi,Marianela Candolfi,Weidong Xiong,Weidong Xiong,Hikmat Assi,Hikmat Assi,Kader Yagiz,Kader Yagiz,Matthew R. Edwards,Kathrin S. Michelsen,Kurt M. Kroeger,Kurt M. Kroeger,Chunyan Liu,Chunyan Liu,A.K.M. Ghulam Muhammad,A.K.M. Ghulam Muhammad,Mary C. Clark,Mary C. Clark,Moshe Arditi,Begonya Comin-Anduix,Antoni Ribas,Pedro R. Lowenstein,Maria G. Castro +26 more
TL;DR: Evidence is provided for the molecular and cellular mechanisms that support the rationale for the clinical implementation of antibrain cancer immunotherapies in combination with tumor killing approaches in order to elicit effective antitumor immune responses, and thus, will impact clinical neuro-oncology practice.