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Glioma T cell

Jiawen Qian, Chen Wang, Bo Wang, Jiao Yang, Yuedi Wang, Feifei Luo, Junying Xu, Chujun Zhao, Ronghua Liu, Yiwei Chu
BACKGROUND: PD-L1 is an immune inhibitory receptor ligand that leads to T cell dysfunction and apoptosis by binding to its receptor PD-1, which works in braking inflammatory response and conspiring tumor immune evasion. However, in gliomas, the cause of PD-L1 expression in the tumor microenvironment is not yet clear. Besides, auxiliary biomarkers are urgently needed for screening possible responsive glioma patients for anti-PD-1/PD-L1 therapies. METHODS: The distribution of tumor-infiltrating T cells and PD-L1 expression was analyzed via immunofluorescence in orthotopic murine glioma model...
October 17, 2018: Journal of Neuroinflammation
Xiudong Guan, Lanxin Luo, Gulnaz Begum, Gary Kohanbash, Qingkun Song, Aparna Rao, Nduka Amankulor, Baoshan Sun, Dandan Sun, Wang Jia
BACKGROUND: Sodium/hydrogen exchanger 1 (NHE1), encoded by the SLC9A1 gene (SoLute Carrier family 9A1) in humans, is the main H+ efflux mechanism in maintaining alkaline intracellular pH (pHi ) and Warburg effects in glioma. However, to date, there are no clinical studies exploring pharmacological inhibition of NHE1 protein in cancer treatment. In this study, we investigated NHE1 expression in gliomas and its relationship with glioma clinical outcome. METHODS: The Chinese Glioma Genome Atlas (CGGA) dataset containing transcriptome sequencing data of 325 glioma samples and the Cancer Genome Atlas (TCGA) with 698 glioma mRNAseq data were analyzed in this study...
October 17, 2018: Journal of Experimental & Clinical Cancer Research: CR
Jonathan A Lubin, Paul A Clark, John S Kuo
No abstract text is available yet for this article.
November 1, 2018: Neurosurgery
Jun Wei, Anantha Marisetty, Brett Schrand, Konrad Gabrusiewicz, Yuuri Hashimoto, Martina Ott, Zacharia Grami, Ling-Yuan Kong, Xiaoyang Ling, Hillary G Caruso, Shouhao Zhou, Y Alan Wang, Gregory N Fuller, Jason T Huse, Eli Gilboa, Nannan Kang, Xingxu Huang, Roel Verhaak, Shulin Li, Amy B Heimberger
Glioblastoma is highly enriched with macrophages, and osteopontin (OPN) expression levels correlate with glioma grade and the degree of macrophage infiltration, thus we studied whether OPN plays a crucial role in immune modulation. Quantitative PCR, immune blotting, and ELISA were used to determine OPN expression. Knockdown of OPN was achieved using complementary siRNA, shRNA and CRISPR/CAS9 techniques followed by a series of in vitro functional migration and immunological assays. OPN gene-deficient mice were used to examine the roles of non-tumor-derived OPN on survival of mice harboring intracranial gliomas...
October 11, 2018: Journal of Clinical Investigation
Yibo Yin, Alina C Boesteanu, Zev A Binder, Chong Xu, Reiss A Reid, Jesse L Rodriguez, Danielle R Cook, Radhika Thokala, Kristin Blouch, Bevin McGettigan-Croce, Logan Zhang, Christoph Konradt, Alexandria P Cogdill, M Kazim Panjwani, Shuguang Jiang, Denis Migliorini, Nadia Dahmane, Avery D Posey, Carl H June, Nicola J Mason, Zhiguo Lin, Donald M O'Rourke, Laura A Johnson
We generated two humanized interleukin-13 receptor α2 (IL-13Rα2) chimeric antigen receptors (CARs), Hu07BBz and Hu08BBz, that recognized human IL-13Rα2, but not IL-13Rα1. Hu08BBz also recognized canine IL-13Rα2. Both of these CAR T cell constructs demonstrated superior tumor inhibitory effects in a subcutaneous xenograft model of human glioma compared with a humanized EGFRvIII CAR T construct used in a recent phase 1 clinical trial ( NCT02209376). The Hu08BBz demonstrated a 75% reduction in orthotopic tumor growth using low-dose CAR T cell infusion...
December 21, 2018: Molecular Therapy Oncolytics
Kui Zhang, Gang Fu, Guangzhao Pan, Chongyang Li, Li Shen, Renjian Hu, Shunqin Zhu, Yibiao Chen, Hongjuan Cui
Glioma is the most common and malignant form of primary brain tumour, and is characterised by high proliferation and extensive invasion and neurological destruction. Demethylzeylasteral (T-96), which is extracted from Tripterygium wilfordii, is considered to have immunosuppressive, anti-inflammatory and anti-angiogenic effects. Here, the anti-tumour effect of T-96 on glioma was evaluated. Our results demonstrated that T-96 significantly inhibited glioma cell growth and induced cell cycle arrest in G1 phase but did not induce apoptosis...
October 10, 2018: Cell Death & Disease
Kamalakannan Palanichamy, John R Jacob, Kevin T Litzenberg, Abhik Ray-Chaudhury, Arnab Chakravarti
BACKGROUND: The goal of this study is to identify and characterize treatment resistant tumor initiating cells (TRTICs) using orthotopic xenografts. METHODS: TRTICs were enriched from GBM cell lines using mouse xenografts treated with fractionated doses of radiation and temozolomide. TRTICs were characterized by neurosphere clonogenicity and self-renewal, serial xenotransplantation, differentiation potential, and mRNA & miRNA transcriptomic profiling. We use an unbiased approach to identify antigens encoding TRTIC and glioma stem cells (GSC) populations...
September 27, 2018: EBioMedicine
Carla Danussi, Jason T Huse
Loss-of-function mutations of the chromatin regulator ATRX (α-thalassemia mental retardation X-linked) occur frequently in diffuse gliomas, but the molecular mechanisms by which ATRX inactivation promotes oncogenesis remain unclear. We recently reported that Atrx deficiency drives glioma-relevant phenotypes, such as increased motility and astrocytic differentiation profiles, by directly modulating epigenomic lanscapes in glioma cells of origin. Our work has significant implications on the role of epigenetic regulator dysfunction in the oncogenic process...
2018: Molecular & Cellular Oncology
Xiudong Guan, Md Nabiul Hasan, Gulnaz Begum, Gary Kohanbash, Karen E Carney, Victoria M Pigott, Anders I Persson, Maria G Castro, Wang Jia, Dandan Sun
The weak immunogenicity of gliomas presents a barrier for effective immunotherapy. Na/H exchanger isoform 1 (NHE1) maintains alkaline intracellular pH (pHi ) of glioma cells and acidic microenvironment. In addition, NHE1 is expressed in tumor-associated microglia and tumor-associated macrophages (TAMs) and involved in protumoral communications between glioma and TAMs. Therefore, we hypothesize that NHE1 plays a role in developing tumor resistance and immunosuppressive tumor microenvironment. In this study, we investigated the efficacy of pharmacological inhibition of NHE1 on combinatorial therapies...
September 27, 2018: Cell Death & Disease
Elias J Sayour, Adam Grippin, Gabriel De Leon, Brian Stover, Maryam Rahman, Aida Karachi, Brandon Wummer, Ginger Moore, Paul Castillo-Caro, Kristianna Fredenburg, Matthew R Sarkisian, Jianping Huang, Loic P Deleyrolle, Bikash Sahay, Sheila Carrera-Justiz, Hector R Mendez-Gomez, Duane A Mitchell
Translation of nanoparticles (NPs) into human clinical trials for patients with refractory cancers has lagged due to unknown biologic reactivities of novel NP designs. To overcome these limitations, simple well-characterized mRNA lipid-NPs have been developed as cancer immunotherapeutic vaccines. While the preponderance of RNA lipid-NPs encoding for tumor-associated antigens or neoepitopes have been designed to target lymphoid organs, they remain encumbered by the profound intratumoral and systemic immunosuppression that may stymie an activated T cell response...
September 27, 2018: Nano Letters
Giuseppe Ferrauto, Enza Di Gregorio, Vincent Auboiroux, Manuel Petit, François Berger, Silvio Aime, Hana Lahrech
In glioma, the acidification of the extracellular tumor microenvironment drives proliferation, angiogenesis, immunosuppression, invasion and chemoresistance. Therefore, quantification of glioma extracellular pH (pHe) is of crucial importance. This study is focused on the application of the YbHPDO3A (ytterbium 1,4,7-triscarboxymethyl-1,4,7,10-tetraazacyclododecane) probe for in vivo glioma pHe quantification using chemical exchange saturation transfer (CEST)-MRI and its correlation with tumor metabolism assessed by immunohistochemistry...
September 5, 2018: NMR in Biomedicine
Fan Wang, QianXue Chen
Context: Results from recent molecular epidemiologic studies suggest that the timeless genes play a role in tumorigenesis, possibly by influencing cell cycle or other pathways relevant to cancer. Aims: The aim of this study was to explore the expression level of the timeless gene in human glioma. Subjects and Methods: Using immunohistochemical staining, methylation-specific polymerase chain reaction techniques, we examined the expression of the timeless gene in 94 gliomas...
September 2018: Journal of Cancer Research and Therapeutics
Liangbo Han, Huaqiang Liu, Jinfeng Wu, Jinkai Liu
BACKGROUND The aim of this study was to assess the utility of miR-126 in promoting malignant glioma progression and determine if miR-126 might be a target for malignant glioma treatment. MATERIAL AND METHODS The expression of miR-126 in malignant glioma tissues and cells was detected by reverse transcription polymerase chain reaction (RT-PCR). Western blot analysis was used to detect changes in protein levels. Transwell assay was applied to assess the migration and invasion in vitro. Luciferase reporter assay was used to confirm the binding of miR-126 and mature T cell proliferation 1 (MTCP1)...
September 20, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Laura R Díaz, Elena Saavedra-López, Leire Romarate, Izaskun Mitxitorena, Paola V Casanova, George P Cribaro, José M Gallego, Ana Pérez-Vallés, Jerónimo Forteza-Vila, Clara Alfaro-Cervello, José M García-Verdugo, Carlos Barcia, Carlos Barcia
Since the proper activation of T cells requires the physical interaction with target cells through the formation of immunological synapses (IS), an alteration at this level could be a reason why tumors escape the immune response. As part of their life cycle, it is thought that T cells alternate between a static phase, the IS, and a dynamic phase, the immunological kinapse (IK), depending on high or low antigen sensing. Our investigation performed in tissue samples of human glioma shows that T cells are able to establish synapsing interactions not only with glioma tumorigenic cells, but also with stromal myeloid cells...
September 20, 2018: JCI Insight
Sonja Schötterl, Stephan M Huber, Hans Lentzen, Michel Mittelbronn, Ulrike Naumann
Viscum album L. extracts (VE) are applied as complementary cancer therapeutics for more than one century. Extracts contain several compounds like mistletoe lectins (ML) 1-3 and viscotoxins, but also several minor ingredients. Since ML-1 has been described as one of the main active components harboring antitumor activity, purified native or recombinant ML-1 has been also used in clinical trials in the last years. The present study examined and compared the immunoboosting effects of three ML-1 containing drugs (the extract ISCADOR Qu, the recombinant ML-1 Aviscumine, and purified native ML-1) in the context of the T-cell mediated killing of glioma cells...
2018: Evidence-based Complementary and Alternative Medicine: ECAM
Alice L Hung, Russell Maxwell, Debebe Theodros, Zineb Belcaid, Dimitrios Mathios, Andrew S Luksik, Eileen Kim, Adela Wu, Yuanxuan Xia, Tomas Garzon-Muvdi, Christopher Jackson, Xiaobu Ye, Betty Tyler, Mark Selby, Alan Korman, Bryan Barnhart, Su-Myeong Park, Je-In Youn, Tamrin Chowdhury, Chul-Kee Park, Henry Brem, Drew M Pardoll, Michael Lim
The use of inhibitory checkpoint blockade in the management of glioblastoma has been studied in both preclinical and clinical settings. TIGIT is a novel checkpoint inhibitor recently discovered to play a role in cancer immunity. In this study, we sought to determine the effect of anti-PD-1 and anti-TIGIT combination therapy on survival in a murine glioblastoma (GBM) model, and to elucidate the underlying immune mechanisms. Using mice with intracranial GL261-luc+ tumors, we found that TIGIT expression was upregulated on CD8+ and regulatory T cells (Tregs) in the brain compared to draining cervical lymph nodes (CLN) and spleen...
2018: Oncoimmunology
Clarissa A Whitehead, Hong P T Nguyen, Andrew P Morokoff, Rodney B Luwor, Lucia Paradiso, Andrew H Kaye, Theo Mantamadiotis, Stanley S Stylli
The most common primary central nervous system tumor in adults is the glioblastoma multiforme (GBM). The highly invasive nature of GBM cells is a significant factor resulting in the inevitable tumor recurrence and poor patient prognosis. Tumor cells utilize structures known as invadopodia to faciliate their invasive phenotype. In this study, utilizing an array of techniques, including gelatin matrix degradation assays, we show that GBM cell lines can form functional gelatin matrix degrading invadopodia and secrete matrix metalloproteinase 2 (MMP-2), a known invadopodia-associated matrix-degrading enzyme...
September 13, 2018: Translational Oncology
Courtney S Malo, Roman H Khadka, Katayoun Ayasoufi, Fang Jin, Jackson E AbouChehade, Michael J Hansen, Raymond Iezzi, Kevin D Pavelko, Aaron J Johnson
Glioblastoma (GBM) is a lethal cancer of the central nervous system with a median survival rate of 15 months with treatment. Thus, there is a critical need to develop novel therapies for GBM. Immunotherapy is emerging as a promising therapeutic strategy. However, current therapies for GBM, in particular anti-angiogenic therapies that block vascular endothelial growth factor (VEGF), may have undefined consequences on the efficacy of immunotherapy. While this treatment is primarily prescribed to reduce tumor vascularization, multiple immune cell types also express VEGF receptors, including the most potent antigen-presenting cell, the dendritic cell (DC)...
2018: Frontiers in Oncology
T A M Bouwens van der Vlis, J M Kros, D A M Mustafa, R T A van Wijck, L Ackermans, P M van Hagen, P J van der Spek
The human complement system is represents the main effector arm of innate immunity and its ambivalent function in cancer has been subject of ongoing dispute. Glioma stem-like cells (GSC) residing in specific niches within glioblastomas (GBM) are capable of self-renewal and tumor proliferation. Recent data are indicative of the influence of the complement system on the maintenance of these cells. It appears that the role of the complement system in glial tumorigenesis, particularly its influence on GSC niches and GSC maintenance, is significant and warrants further exploration for therapeutic interventions...
September 12, 2018: Acta Neuropathologica Communications
Alex Shimura Yamashita, Marina da Costa Rosa, Alexandra Borodovsky, William T Festuccia, Timothy Chan, Gregory J Riggins
Background: Isocitrate Deyhydrogenase (IDH) mutant gliomas are comprised of the majority of grade II-III gliomas and nearly all secondary glioblastomas. These progressive gliomas arise from mutations in IDH1 or IDH2 that pathologically produces D-2-hydroxyglutarate (2HG). 2-HG interferes with cell reactions using alpha ketoglutarate leading to a hypermethylated genome and epigenetic dysregulation of gene expression initiating tumorigenesis. Methods: Human IDH1 WT and IDH1R132H cell lines and patient derived xenografts (PDX) were used to evaluate the FDA-approved DNA demethylating agent 5-Azacytidine (5-Aza)...
September 3, 2018: Neuro-oncology
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