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https://www.readbyqxmd.com/read/29222400/nkg2d-based-car-t-cells-and-radiotherapy-exert-synergistic-efficacy-in-glioblastoma
#1
Tobias Weiss, Michael Weller, Matthias Guckenberger, Charles L Sentman, Patrick Roth
Chimeric antigen receptor (CAR) T cell therapy is an emerging immunotherapy against several malignancies including glioblastoma, the most common and most aggressive malignant primary brain tumor in adults. The challenges in solid tumor immunotherapy comprise heterogenously expressed tumor target antigens and restricted trafficking of CAR T cells to and impaired long-term persistence at the tumor site, as well as the unaddressed integration of CAR T cell therapy into conventional anti-cancer treatments. We addressed these questions using a NKG2D-based chimeric antigen receptor construct (chNKG2D) in fully immunocompetent orthotopic glioblastoma mouse models...
December 8, 2017: Cancer Research
https://www.readbyqxmd.com/read/29222323/graft-versus-tumor-effects-and-why-people-relapse
#2
REVIEW
J H Frederik Falkenburg, Inge Jedema
Graft-versus-tumor (GVT) reactivity mediated by donor T cells in the context of allogeneic stem cell transplantation (alloSCT) is one of the most potent forms of cellular immunotherapy. The antitumor effect against hematologic malignancies is mediated by a polyclonal T-cell response targeting polymorphic antigens expressed on hematopoietic tissues of the recipient, leaving donor hematopoiesis in the patient after transplantation unharmed. Fortunately, hematopoietic tissues (including malignant hematopoietic cell populations) are relatively susceptible to T-cell recognition...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222313/developing-t-cell-therapies-for-lymphoma-without-receptor-engineering
#3
REVIEW
Melanie Grant, Catherine M Bollard
T-cell therapy has emerged from the bench for the treatment of patients with lymphoma. Responses to T-cell therapeutics are regulated by multiple factors, including the patient's immune system status and disease stage. Outside of engineering of chimeric antigen receptors and artificial T-cell receptors, T-cell therapy can be mediated by ex vivo expansion of antigen-specific T cells targeting viral and/or nonviral tumor-associated antigens. These approaches are contributing to enhanced clinical responses and overall survival...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222312/harnessing-the-power-of-the-immune-system-in-non-hodgkin-lymphoma-immunomodulators-checkpoint-inhibitors-and-beyond
#4
REVIEW
Stephen M Ansell
Non-Hodgkin lymphoma is a malignancy of B lymphocytes that typically infiltrate sites of disease, including the lymph nodes, spleen, and bone marrow. Beyond the presence of malignant cells, many immune cells are also present within the tumor microenvironment. Although these immune cells have the potential to regulate the growth of malignant B cells, intratumoral immune cells are unable to eradicate lymphoma cells and most patients with lymphoma have clinical evidence of disease progression. Recent data have identified some of the mechanisms that account for the suppressed antitumor immune response and have created opportunities for treatment to overcome the deficiencies...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222311/role-of-the-microenvironment-across-histological-subtypes-of-nhl
#5
REVIEW
Karin Tarte
Recent progress in next-generation sequencing strategies has revealed the genetic landscape of B-cell non-Hodgkin lymphoma, but the tumor microenvironment is increasingly recognized as crucial to sustaining malignant B-cell survival and growth, subclonal evolution, and drug resistance. The tumor niche is made up of a dynamic and organized network of strongly heterogeneous immune and stromal cell subsets characterized by specific phenotypic, transcriptomic, and functional features. Nonmalignant cell recruitment and plasticity are dictated by lymphoma B cells, which convert their surrounding microenvironment into a supportive niche...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222305/biology-of-cns-lymphoma-and-the-potential-of-novel-agents
#6
REVIEW
James L Rubenstein
Primary and secondary CNS lymphomas are aggressive brain tumors that pose an immense challenge to define in terms of molecular pathogenesis, as well as to effectively treat. During the past 10 years improvements in survival have been achieved with the implementation of anti-CD20 immunotherapy and optimization of dose-intensive consolidation strategies. The applications of whole-exome sequencing, comparative genomic hybridization, transcriptional profiling, and examination of the tumor microenvironment, particularly in the context of clinical investigation, provide insights that create a roadmap for the development and implementation of novel targeted agents for this disease...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222272/signaling-pathways-and-immune-evasion-mechanisms-in-classical-hodgkin-lymphoma
#7
REVIEW
W Robert Liu, Margaret A Shipp
Classical Hodgkin lymphoma (cHL) is an unusual B-cell-derived malignancy in which rare malignant Hodgkin and Reed-Sternberg (HRS) cells are surrounded by an extensive but ineffective inflammatory/immune cell infiltrate. This striking feature suggests that malignant HRS cells escape immunosurveillance and interact with immune cells in the cancer microenvironment for survival and growth. We previously found that cHLs have a genetic basis for immune evasion: near-uniform copy number alterations of chromosome 9p24...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222190/loss-of-dna-repair-drives-neoantigen-renewal-and-inhibits-tumor-growth
#8
(no author information available yet)
DNA mismatch repair in tumors promotes enhanced immune surveillance.
December 8, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/29222188/myc-induces-immune-suppression-to-promote-lung-tumorigenesis
#9
(no author information available yet)
MYC promotes angiogenesis, inflammation, and immune suppression to accelerate KRASG12D tumor growth.
December 8, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/29222071/hdac11-is-a-regulator-of-diverse-immune-functions
#10
REVIEW
Cansu Yanginlar, Colin Logie
Histone deacetylases deacetylate histone and non-histone protein targets. Aberrant HDAC expression and function have been observed in several diseases, which makes these enzymes attractive treatment targets. Here, we summarize recent literature that addresses the roles of HDAC11 on the regulation of different immune cells including neutrophils, myeloid derived suppressor cells and T-cells. HDAC11 was initially identified as a negative regulator of the well-known anti-inflammatory cytokine IL-10. Hence, antagonizing HDAC11 activity may have anti-tumor potential, whereas activating HDAC11 may be useful to treat chronic inflammation or autoimmunity...
December 5, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29222039/the-role-of-stat3-in-leading-the-crosstalk-between-human-cancers-and-the-immune-system
#11
Yu Wang, Yicheng Shen, Sinan Wang, Qiang Shen, Xuan Zhou
The development and progression of human cancers are continuously and dynamically regulated by intrinsic and extrinsic factors. As a converging point of multiple oncogenic pathways, signal transducer and activator of transcription 3 (STAT3) is constitutively activated both in tumor cells and tumor-infiltrated immune cells. Activated STAT3 persistently triggers tumor progression through direct regulation of oncogenic gene expression. Apart from its oncogenic role in regulating gene expression in tumor cells, STAT3 also paves the way for human cancer growth through immunosuppression...
December 5, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29222012/macrophage-immunomodulatory-activity-of-the-polysaccharide-isolated-from-collybia-radicata-mushroom
#12
Yufeng Wang, Youqiu Tian, Jiangjuan Shao, Xu Shu, Jinxia Jia, Xiaojie Ren, Yue Guan
Polysaccharides from Collybia radicata mushroom (CRP) possess many functions, such as antiviral, anti-aging and hypolipidemic activities. However, little is known about their immunomodulatory activity. To address this issue, we did a thorough research into their immune effects on murine macrophages. The results showed that the 14942Da polysaccharide not only obviously improved the proliferation and phagocytosis of macrophages, but also induced the secretion of nitric oxide (NO), inducible nitric oxide synthase (iNOS) and cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin factors (IL-1β, IL-6 and IL-10)...
December 5, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29221287/anti-cancer-activity-of-dose-fractioned-mpe-bevacizumab-regimen-is-paralleled-by-immune-modulation-in-advanced-squamous-nslc-patients
#13
Pierpaolo Pastina, Valerio Nardone, Stefania Croci, Giuseppe Battaglia, Francesca Vanni, Cristiana Bellan, Marcella Barbarino, Veronica Ricci, Susan Costantini, Francesca Capone, Cirino Botta, Mayra Rachele Zarone, Gabriella Misso, Mariarosaria Boccellino, Michele Caraglia, Antonio Giordano, Piero Paladini, Pierfrancesco Tassone, Pierosandro Tagliaferri, Maria Grazia Cusi, Luigi Pirtoli, Pierpaolo Correale
Background: Results from the BEVA2007 trial, suggest that the metronomic chemotherapy regimen with dose-fractioned cisplatin and oral etoposide (mPE) +/- bevacizumab, a monoclonal antibody to the vascular endothelial growth factor (VEGF), shows anti-angiogenic and immunological effects and is a safe and active treatment for metastatic non-small cell lung cancer (mNSCLC) patients. We carried out a retrospective analysis aimed to evaluate the antitumor effects of this treatment in a subset of patients with squamous histology...
September 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/29221220/significant-benefit-of-nivolumab-treating-pd-l1-positive-metastatic-pulmonary-carcinosarcoma-a-case-report-and-literature-review
#14
Zhe Zhang, Yishan Chen, Mingxia Ma, Junli Hao, Rui Ding, Lixin Han, Jiayun Zou, Lina Zhang, Qin Meng, Xiujuan Qu, Yunpeng Liu, Mingfang Zhao
Immunotherapy has recently become a new focus for the treatment of malignant tumors following the surgery, chemotherapy, radiotherapy, and molecular targeted therapy. Nivolumab, a human monoclonal antibody, is the first programmed cell death protein-1 (PD-1) inhibitor, which can prohibit the interaction of its ligand (PD-L1), restoring the immune response of T cells, and enhancing the recognition of tumor cells by the immune system. Pulmonary carcinosarcoma is an uncommon but highly aggressive tumor type with a poor prognosis...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29221197/rank-expression-in-ebv-positive-nasopharyngeal-carcinoma-metastasis-a-ready-to-treat-target
#15
Carlo Resteghini, Salvatore Alfieri, Pasquale Quattrone, Francesca Dominoni, Giovanna Garzone, Ester Orlandi, Laura Locati, Cristiana Bergamini, Donata Galbiati, Nicola Alessandro Iacovelli, Carlo Fallai, Lisa Licitra, Paolo Bossi
Epstein Barr Virus (EBV) related Nasopharyngeal Carcinoma (NPC), is an highly chemo- and radiosensitive endemic malignancy in southeast Asia. More than one third of locally advanced cases relapse after curative treatment, especially because of bone, liver and lung metastases. Lymphocyte sub-populations favour EBV-associated carcinogenesis and tumour progression and several strategies aim to reverse this phenomenon. Receptor activator of NF-kB (RANK) and its Ligand (RANKL), key regulator of bone metabolisms, are expressed in several malignancies and tumor-infiltrating Tregs...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29221172/the-prognostic-value-of-inflammation-based-scores-in-advanced-hepatocellular-carcinoma-patients-prior-to-treatment-with-sorafenib
#16
Guillaume Conroy, Julia Salleron, Arthur Belle, Mouni Bensenane, Abdelbasset Nani, Ahmet Ayav, Didier Peiffert, Anthony Lopez, Cédric Baumann, Hélène Barraud, Jean-Pierre Bronowicki
Background and Aims: The multikinase inhibitor sorafenib is the only currently approved drug for the indication of advanced hepatocellular carcinoma (HCC). It provides a limited gain in survival time but is frequently associated with adverse events. We currently lack simple prognostic factors in sorafenib-treated HCC patients. Various inflammation-based scores (IBSs) have been evaluated as predictors of tumor recurrence and survival in various malignancies (including HCC). The objective of the present study was to determine the prognostic value of IBSs for overall survival (OS) in advanced HCC patients prior to the initiation of sorafenib therapy...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29221117/inhibition-of-chemerin-cmklr1-axis-in-neuroblastoma-cells-reduces-clonogenicity-and-cell-viability-in-vitro-and-impairs-tumor-growth-in-vivo
#17
Conny Tümmler, Igor Snapkov, Malin Wickström, Ugo Moens, Linda Ljungblad, Lotta Helena Maria Elfman, Jan-Olof Winberg, Per Kogner, John Inge Johnsen, Baldur Sveinbjørnsson
Pro-inflammatory cells, cytokines, and chemokines are essential in promoting a tumor supporting microenvironment. Chemerin is a chemotactic protein and a natural ligand for the receptors CMKLR1, GPR1, and CCRL2. The chemerin/CMKLR1 axis is involved in immunity and inflammation, and it has also been implicated in obesity and cancer. In neuroblastoma, a childhood tumor of the peripheral nervous system we identified correlations between high CMKLR1 and GPR1 expression and reduced overall survival probability. CMKLR1, GPR1, and chemerin RNA and protein were detected in neuroblastoma cell lines and neuroblastoma primary tumor tissue...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29220536/cd36-deficiency-attenuates-immune-mediated-hepatitis-in-mice-by-modulating-the-proapoptotic-effects-of-cxcl10
#18
Che Xu, Chen Zhang, Jie Ji, Chao Wang, Jing Yang, Biao Geng, Ting Zhao, Hong Zhou, Xianmin Mu, Jinshun Pan, Shi Hu, Yuanfang Lv, Xingguo Chen, Hao Wen, Qiang You
The scavenger receptor, CD36, recognizes a diverse set of ligands, and has been implicated in a wide variety of normal and pathological processes, including lipid metabolism, angiogenesis, atherosclerosis, and phagocytosis. In particular, recent findings have demonstrated its crucial functions in sterile inflammation and tumor metastasis. However, the role of CD36 in immune-mediated hepatitis remains unclear. Concanavalin A (Con A)-induced liver injury is a well-established experimental T cell-mediated hepatitis...
December 8, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29220291/emerging-targeted-and-immune-based-therapies-in-sarcoma
#19
Seth M Pollack, Matthew Ingham, Matthew B Spraker, Gary K Schwartz
Soft tissue and bone sarcomas are malignancies of mesenchymal origin, and more than 50 subtypes are defined. For most sarcomas, locally advanced or unresectable disease is still treated with cytotoxic chemotherapy. Recently, our understanding of subtype-specific cancer biology has expanded, and it has revealed distinct molecular alterations responsible for tumor initiation and progression. These findings have motivated the development of targeted therapies that are being evaluated in subtype-specific or biomarker-driven clinical trials...
December 8, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29219147/mitochondrial-metabolism-and-cancer
#20
REVIEW
Paolo Ettore Porporato, Nicoletta Filigheddu, José Manuel Bravo-San Pedro, Guido Kroemer, Lorenzo Galluzzi
Glycolysis has long been considered as the major metabolic process for energy production and anabolic growth in cancer cells. Although such a view has been instrumental for the development of powerful imaging tools that are still used in the clinics, it is now clear that mitochondria play a key role in oncogenesis. Besides exerting central bioenergetic functions, mitochondria provide indeed building blocks for tumor anabolism, control redox and calcium homeostasis, participate in transcriptional regulation, and govern cell death...
December 8, 2017: Cell Research
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