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Immunology glioblastoma

Cristina Maccalli, Giorgio Parmiani, Soldano Ferrone
Cancer-initiating cells (CICs) represent a relatively rare subpopulation of cells endowed with self-renewal, stemness properties, tumorigenicity in immunodeficient mice, and resistance to standard therapies as well as to immunotherapy. Here, we review the biological and immunological characteristics of CICs with special focus on the immunomodulating mechanisms they utilize to escape from immunosurveillance. The recently developed immunotherapeutic strategies have yielded remarkable clinical results in many types of tumors, indicating that indeed a patient's immune system can mount an immune response, which is effective in controlling tumor growth...
April 2017: Immunological Investigations
Alireza Vakilian, Hossein Khorramdelazad, Parisa Heidari, Zahra Sheikh Rezaei, Gholamhossein Hassanshahi
Glioblastoma multiform (GBM) is described as one of the most frequent primary brain tumors. These types of malignancies constitute only 15% of all primary brain tumors. Despite, extensive developments on effective therapeutic methods during the 20th century as well as the first decade of the present century (21st), the median survival rate for patients suffering from GBM is only approximately 15 months, even in response to multi-modal therapy. numerous types of reticuloendothelial system cells such as macrophages and microglial cells occupied within both GBM and also normal surrounding tissues...
February 2017: Neurochemistry International
Dimitrios Mathios, Jennifer E Kim, Antonella Mangraviti, Jillian Phallen, Chul-Kee Park, Christopher M Jackson, Tomas Garzon-Muvdi, Eileen Kim, Debebe Theodros, Magdalena Polanczyk, Allison M Martin, Ian Suk, Xiaobu Ye, Betty Tyler, Chetan Bettegowda, Henry Brem, Drew M Pardoll, Michael Lim
The immunosuppressive effects of chemotherapy present a challenge for designing effective cancer immunotherapy strategies. We hypothesized that although systemic chemotherapy (SC) exhibits negative immunologic effects, local chemotherapy (LC) can potentiate an antitumor immune response. We show that LC combined with anti-programmed cell death protein 1 (PD-1) facilitates an antitumor immune response and improves survival (P < 0.001) in glioblastoma. LC-treated mice had increased infiltration of tumor-associated dendritic cells and clonal expansion of antigen-specific T effector cells...
December 21, 2016: Science Translational Medicine
Evan K Winograd, Michael J Ciesielski, Robert A Fenstermaker
Glioblastoma is the most common primary brain cancer. Aggressive treatment with surgery, radiation therapy and chemotherapy provides limited overall survival benefit. Glioblastomas have a formidable tumor microenvironment that is hostile to immunological effector cells and these cancers produce profound systemic immunosuppression. However, surgical resection of these tumors creates conditions that favor the use of immunotherapeutic strategies. Therefore, extensive surgical resection, when feasible, will remain part of the equation to provide an environment in which active specific immunotherapy has the greatest chance of working...
November 2016: Immunotherapy
Jorge Humberto Tapia-Pérez, Robert Preininger, Elmar Kirches, Annegret Reinhold, Jana Butzmann, Sylvia Prilloff, Christian Mawrin, Thomas Schneider
BACKGROUND/AIM: Statins are cholesterol reducers with considerable dose-dependent effect against glioma cells. The apoptotic effect could be increased by combining statins or by adding pioglitazone (PGZ). The last one is an anti-diabetic drug, an agonist of the peroxisome proliferator-activated receptor-gamma (PPARG). We used an animal model to test the effect of such combination in vivo and we investigated the changes on immunological processes. MATERIALS AND METHODS: Thirty-three rats (F344/DuCrl) were anesthetized and glioblastoma (F98) cells were implanted stereotactically...
2016: Anticancer Research
Ian F Pollack, Regina I Jakacki, Lisa H Butterfield, Ronald L Hamilton, Ashok Panigrahy, Daniel P Normolle, Angela K Connelly, Sharon Dibridge, Gary Mason, Theresa L Whiteside, Hideho Okada
Recurrent high-grade gliomas (HGGs) of childhood have an exceedingly poor prognosis with current therapies. Accordingly, new treatment approaches are needed. We initiated a pilot trial of vaccinations with peptide epitopes derived from glioma-associated antigens (GAAs) overexpressed in these tumors in HLA-A2+ children with recurrent HGG that had progressed after prior treatments. Peptide epitopes for three GAAs (EphA2, IL13Rα2, survivin), emulsified in Montanide-ISA-51, were administered subcutaneously adjacent to intramuscular injections of poly-ICLC every 3 weeks for 8 courses, followed by booster vaccines every 6 weeks...
December 2016: Journal of Neuro-oncology
Haouraa Mostafa, Andrej Pala, Josef Högel, Michal Hlavac, Elvira Dietrich, M Andrew Westhoff, Lisa Nonnenmacher, Timo Burster, Michael Georgieff, C Rainer Wirtz, E Marion Schneider
BACKGROUND: Glioblastoma multiforme (GBM), a common primary malignant brain tumor, rarely disseminates beyond the central nervous system and has a very bad prognosis. The current study aimed at the analysis of immunological control in individual patients with GBM. METHODS: Immune phenotypes and plasma biomarkers of GBM patients were determined at the time of diagnosis using flow cytometry and ELISA, respectively. RESULTS: Using descriptive statistics, we found that immune anomalies were distinct in individual patients...
2016: Journal of Hematology & Oncology
Joseph P Antonios, Horacio Soto, Richard G Everson, Joey Orpilla, Diana Moughon, Namjo Shin, Shaina Sedighim, William H Yong, Gang Li, Timothy F Cloughesy, Linda M Liau, Robert M Prins
DC vaccination with autologous tumor lysate has demonstrated promising results for the treatment of glioblastoma (GBM) in preclinical and clinical studies. While the vaccine appears capable of inducing T cell infiltration into tumors, the effectiveness of active vaccination in progressively growing tumors is less profound. In parallel, a number of studies have identified negative costimulatory pathways, such as programmed death 1/programmed death ligand 1 (PD-1/PD-L1), as relevant mediators of the intratumoral immune responses...
July 7, 2016: JCI Insight
Mev Dominguez-Valentin, Andrea Gras Navarro, Aminur Mohummad Rahman, Surendra Kumar, Christèle Retière, Elling Ulvestad, Vessela Kristensen, Morten Lund-Johansen, Benedicte Alexandra Lie, Per Øyvind Enger, Gro Njølstad, Einar Kristoffersen, Stein Atle Lie, Martha Chekenya
By affecting immunological presentation, the presence of cytomegalovirus in some glioblastomas may impact progression. In this study, we examined a hypothesized role for natural killer (NK) cells in impacting disease progression in this setting. We characterized 108 glioblastoma patients and 454 healthy controls for HLA-A,-B,-C, NK-cell KIR receptors, and CMV-specific antibodies and correlated these metrics with clinical parameters. Exome sequences from a large validation set of glioblastoma patients and control individuals were examined from in silico databases...
September 15, 2016: Cancer Research
Ji Young Yoo, Alena Cristina Jaime-Ramirez, Chelsea Bolyard, Hongsheng Dai, Tejaswini Nallanagulagari, Jeffrey Wojton, Brian S Hurwitz, Theresa Relation, Tae Jin Lee, Michael T Lotze, Jun-Ge Yu, Jianying Zhang, Carlo M Croce, Jianhua Yu, Michael A Caligiuri, Matthew Old, Balveen Kaur
PURPOSE: Both the proteasome inhibitor bortezomib and an oncolytic herpes simplex virus-1 (oHSV)-expressing GM-CSF are currently FDA approved. Although proteasome blockade can increase oHSV replication, immunologic consequences, and consequent immunotherapy potential are unknown. In this study, we investigated the impact of bortezomib combined with oHSV on tumor cell death and sensitivity to natural killer (NK) cell immunotherapy. EXPERIMENTAL DESIGN: Western blot, flow cytometry, and caspase 3/7 activity assays were used to evaluate the induction of apoptosis/autophagy and/or necroptotic cell death...
November 1, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Or Cohen-Inbar, Menashe Zaaroor
Glioblastoma Multiforme (GBM) is the most common malignant primary brain neoplasm having a mean survival time of <24 months. This figure remains constant, despite significant progress in medical research and treatment. The lack of an efficient anti-tumor immune response and the micro-invasive nature of the glioma malignant cells have been explained by a multitude of immune-suppressive mechanisms, proven in different models. These immune-resistant capabilities of the tumor result in a complex interplay this tumor shares with the immune system...
July 2016: Canadian Journal of Neurological Sciences. le Journal Canadien des Sciences Neurologiques
Roxana Magaña-Maldonado, Elda Georgina Chávez-Cortez, Nora Karen Olascoaga-Arellano, Mariana López-Mejía, Fernando Manuel Maldonado-Leal, Julio Sotelo, Benjamín Pineda
Glioblastoma is the most aggressive tumor in Central Nervous System in adults. Among its features, modulation of immune system stands out. Although immune system is capable of detecting and eliminating tumor cells mainly by cytotoxic T and NK cells, tumor microenvironment suppresses an effective response through recruitment of modulator cells such as regulatory T cells, monocyte-derived suppressor cells, M2 macrophages, and microglia as well as secretion of immunomodulators including IL-6, IL-10, CSF-1, TGF-β, and CCL2...
2016: BioMed Research International
Mira A Patel, Jennifer E Kim, Debebe Theodros, Ada Tam, Esteban Velarde, Christina M Kochel, Brian Francica, Thomas R Nirschl, Ali Ghasemzadeh, Dimitrios Mathios, Sarah Harris-Bookman, Christopher C Jackson, Christina Jackson, Xiaobu Ye, Phuoc T Tran, Betty Tyler, Vladimir Coric, Mark Selby, Henry Brem, Charles G Drake, Drew M Pardoll, Michael Lim
BACKGROUND: Glioblastoma (GBM) is a poorly immunogenic neoplasm treated with focused radiation. Immunotherapy has demonstrated synergistic survival effects with stereotactic radiosurgery (SRS) in murine GBM. GITR is a co-stimulatory molecule expressed constitutively on regulatory T-cells and by effector T-cells upon activation. We tested the hypothesis that anti-GITR monoclonal antibody (mAb) and SRS together would confer an immune-mediated survival benefit in glioma using the orthotopic GL261 glioma model...
2016: Journal for Immunotherapy of Cancer
Konrad Gabrusiewicz, Benjamin Rodriguez, Jun Wei, Yuuri Hashimoto, Luke M Healy, Sourindra N Maiti, Ginu Thomas, Shouhao Zhou, Qianghu Wang, Ahmed Elakkad, Brandon D Liebelt, Nasser K Yaghi, Ravesanker Ezhilarasan, Neal Huang, Jeffrey S Weinberg, Sujit S Prabhu, Ganesh Rao, Raymond Sawaya, Lauren A Langford, Janet M Bruner, Gregory N Fuller, Amit Bar-Or, Wei Li, Rivka R Colen, Michael A Curran, Krishna P Bhat, Jack P Antel, Laurence J Cooper, Erik P Sulman, Amy B Heimberger
Glioblastomas are highly infiltrated by diverse immune cells, including microglia, macrophages, and myeloid-derived suppressor cells (MDSCs). Understanding the mechanisms by which glioblastoma-associated myeloid cells (GAMs) undergo metamorphosis into tumor-supportive cells, characterizing the heterogeneity of immune cell phenotypes within glioblastoma subtypes, and discovering new targets can help the design of new efficient immunotherapies. In this study, we performed a comprehensive battery of immune phenotyping, whole-genome microarray analysis, and microRNA expression profiling of GAMs with matched blood monocytes, healthy donor monocytes, normal brain microglia, nonpolarized M0 macrophages, and polarized M1, M2a, M2c macrophages...
2016: JCI Insight
Jun-Ping Liu
This editorial draws attention to the work published by CEPP in 2014-2015 on mechanisms underlying cancer drug resistance, invasion and metastasis. Genetic, genomic and immunological changes in platinum drug resistance and new drug candidates for cancer metastasis are highlighted. Attention is paid to the Epimedium plant drug icariin in glioblastoma invasion, the plant Avicennia marina bioactive compound Naphtho[1,2-b]furan-4,5-dione in breast cancer metastasis, the PI3K inhibitor BEZ235 in colon cancer stem cells, the histone methyltransferase EZH1 inhibitor GSK343 in cervical cancer, and vitamin D3 in prostate cancer...
March 2016: Clinical and Experimental Pharmacology & Physiology
Satoshi Shiina, Masasuke Ohno, Fumiharu Ohka, Shunichiro Kuramitsu, Akane Yamamichi, Akira Kato, Kazuya Motomura, Kuniaki Tanahashi, Takashi Yamamoto, Reiko Watanabe, Ichiro Ito, Takeshi Senga, Michinari Hamaguchi, Toshihiko Wakabayashi, Mika K Kaneko, Yukinari Kato, Vidyalakshmi Chandramohan, Darell D Bigner, Atsushi Natsume
Glioblastoma (GBM) is the most common and lethal primary malignant brain tumor in adults with a 5-year overall survival rate of less than 10%. Podoplanin (PDPN) is a type I transmembrane mucin-like glycoprotein, expressed in the lymphatic endothelium. Several solid tumors overexpress PDPN, including the mesenchymal type of GBM, which has been reported to present the worst prognosis among GBM subtypes. Chimeric antigen receptor (CAR)-transduced T cells can recognize predefined tumor surface antigens independent of MHC restriction, which is often downregulated in gliomas...
March 2016: Cancer Immunology Research
Jonathan B Lamano, Leonel Ampie, Winward Choy, Kartik Kesavabhotla, Joseph D DiDomenico, Daniel E Oyon, Andrew T Parsa, Orin Bloch
Given the continued poor clinical outcomes and refractory nature of glioblastoma multiforme to traditional interventions, immunotherapy is gaining traction due to its potential for specific tumor-targeting and long-term antitumor protective surveillance. Currently, development of glioma immunotherapy relies on overall survival as an endpoint in clinical trials. However, the identification of surrogate immunologic biomarkers can accelerate the development of successful immunotherapeutic strategies. Immunomonitoring techniques possess the potential to elucidate immunological mechanisms of antitumor responses, monitor disease progression, evaluate therapeutic effect, identify candidates for immunotherapy, and serve as prognostic markers of clinical outcome...
March 2016: Journal of Neuro-oncology
E T Wong, E Lok, S Gautam, K D Swanson
No abstract text is available yet for this article.
December 1, 2015: British Journal of Cancer
Anda-Alexandra Calinescu, Neha Kamran, Gregory Baker, Yohei Mineharu, Pedro Ricardo Lowenstein, Maria Graciela Castro
In the last decade, numerous studies of immunotherapy for malignant glioma (glioblastoma multiforme) have brought new knowledge and new hope for improving the prognosis of this incurable disease. Some clinical trials have reached Phase III, following positive outcomes in Phase I and II, with respect to safety and immunological end points. Results are encouraging especially when considering the promise of sustained efficacy by inducing antitumor immunological memory. Progress in understanding the mechanisms of tumor-induced immune suppression led to the development of drugs targeting immunosuppressive checkpoints, which are used in active clinical trials for glioblastoma multiforme...
2015: Immunotherapy
Pu Wang, Xin Yu, Pei-Pei Guan, Jing-Wen Guo, Yue Wang, Yan Zhang, Hang Zhao, Zhan-You Wang
Alzheimer's disease (AD) has been associated with magnesium ion (Mg(2+)) deficits and interleukin-1β (IL-1β) elevations in the serum or brains of AD patients. However, the mechanisms regulating IL-1β expression during Mg(2+) dyshomeostasis in AD remain unknown. We herein studied the mechanism of IL-1β reduction using a recently developed compound, magnesium-L-threonate (MgT). Using human glioblastoma A172 and mouse brain D1A glial cells as an in vitro model system, we delineated the signaling pathways by which MgT suppressed the expression of IL-1β in glial cells...
November 9, 2015: Cellular & Molecular Immunology
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