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Immune evasion

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https://www.readbyqxmd.com/read/28319047/isocitrate-dehydrogenase-mutations-suppress-stat1-and-cd8-t-cell-accumulation-in-gliomas
#1
Gary Kohanbash, Diego A Carrera, Shruti Shrivastav, Brian J Ahn, Naznin Jahan, Tali Mazor, Zinal S Chheda, Kira M Downey, Payal B Watchmaker, Casey Beppler, Rolf Warta, Nduka A Amankulor, Christel Herold-Mende, Joseph F Costello, Hideho Okada
Mutations in the isocitrate dehydrogenase genes IDH1 and IDH2 are among the first genetic alterations observed during the development of lower-grade glioma (LGG). LGG-associated IDH mutations confer gain-of-function activity by converting α-ketoglutarate to the oncometabolite R-2-hydroxyglutarate (2HG). Clinical samples and gene expression data from The Cancer Genome Atlas (TCGA) demonstrate reduced expression of cytotoxic T lymphocyte-associated genes and IFN-γ-inducible chemokines, including CXCL10, in IDH-mutated (IDH-MUT) tumors compared with IDH-WT tumors...
March 20, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28317380/systems-biology-reveals-ns4b-cyclophilin-a-interaction-a-new-target-to-inhibit-yfv-replication
#2
Alessandra Vidotto, Ana T S Morais, Milene Rocha Ribeiro, Carolina C Pacca, Ana C B Terzian, Laura H V G Gil, Ronaldo Mohana-Borges, Philippe Gallay, Mauricio L Nogueira
Yellow fever virus (YFV) replication is highly dependent upon host cell factors. YFV NS4B is reported to be involved in viral replication and immune evasion. Here, interactions between NS4B and human proteins were determined using a GST pull-down assay and analyzed using 1- DE and LC-MS/MS. We present a total of 207 proteins confirmed using Scaffold 3 Software. Cyclophilin A (CypA), a protein which has been shown to be necessary for the positive regulation of flavivirus replication, was identified as a possible NS4B partner...
March 20, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28314758/immune-checkpoint-dysfunction-in-medium-and-large-vessel-vasculitis
#3
Ryu Watanabe, Hui Zhang, Gerald Berry, Jorg J Goronzy, Cornelia M Weyand
Giant cell arteritis (GCA) is a granulomatous vasculitis of the aorta and its medium-sized branch vessels. CD4 T-cells, macrophages and dendritic cells build granulomatous infiltrates that injure the vessel wall and elicit a maladaptive response-to-injury. Pathologic consequences include fragmentation of elastic membranes, destruction of the medial layer, microvascular neoangiogenesis, massive outgrowth of myofibroblasts, and lumen-occlusive intimal hyperplasia. Antigens have been suspected to drive the local activation of vasculitogenic CD4 T-cells, but recent data suggest a more generalized defect in the threshold setting of such T-cells, rendering them hyperreactive...
March 17, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28304339/the-five-immune-forces-impacting-dna-based-cancer-immunotherapeutic-strategy
#4
REVIEW
Suneetha Amara, Venkataswarup Tiriveedhi
DNA-based vaccine strategy is increasingly realized as a viable cancer treatment approach. Strategies to enhance immunogenicity utilizing tumor associated antigens have been investigated in several pre-clinical and clinical studies. The promising outcomes of these studies have suggested that DNA-based vaccines induce potent T-cell effector responses and at the same time cause only minimal side-effects to cancer patients. However, the immune evasive tumor microenvironment is still an important hindrance to a long-term vaccine success...
March 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28303129/there-is-a-method-to-the-madness-strategies-to-study-host-complement-evasion-by-lyme-disease-and-relapsing-fever-spirochetes
#5
REVIEW
Ashley L Marcinkiewicz, Peter Kraiczy, Yi-Pin Lin
Lyme disease and relapsing fever are caused by various Borrelia species. Lyme disease borreliae, the most common vector-borne pathogens in both the U.S. and Europe, are transmitted by Ixodes ticks and disseminate from the site of tick bites to tissues leading to erythema migrans skin rash, arthritis, carditis, and neuroborreliosis. Relapsing fever borreliae, carried by ticks and lice, trigger reoccurring fever episodes. Following transmission, spirochetes survive in the blood to induce bacteremia at the early stages of infection, which is thought to promote evasion of the host complement system...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28302645/pd-l1-on-tumor-cells-is-sufficient-for-immune-evasion-in-immunogenic-tumors-and-inhibits-cd8-t-cell-cytotoxicity
#6
Vikram R Juneja, Kathleen A McGuire, Robert T Manguso, Martin W LaFleur, Natalie Collins, W Nicholas Haining, Gordon J Freeman, Arlene H Sharpe
It is unclear whether PD-L1 on tumor cells is sufficient for tumor immune evasion or simply correlates with an inflamed tumor microenvironment. We used three mouse tumor models sensitive to PD-1 blockade to evaluate the significance of PD-L1 on tumor versus nontumor cells. PD-L1 on nontumor cells is critical for inhibiting antitumor immunity in B16 melanoma and a genetically engineered melanoma. In contrast, PD-L1 on MC38 colorectal adenocarcinoma cells is sufficient to suppress antitumor immunity, as deletion of PD-L1 on highly immunogenic MC38 tumor cells allows effective antitumor immunity...
March 16, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28302417/muc1-c-oncoprotein-integrates-a-program-of-emt-epigenetic-reprogramming-and-immune-evasion-in-human-carcinomas
#7
REVIEW
Hasan Rajabi, Donald Kufe
The MUC1 gene evolved in mammalian species to provide protection of epithelia. The transmembrane MUC1 C-terminal subunit (MUC1-C) signals stress to the interior of the epithelial cell and, when overexpressed as in most carcinomas, functions as an oncoprotein. MUC1-C induces the epithelial-mesenchymal transition (EMT) by activating the inflammatory NF-κB p65 pathway and, in turn, the EMT-transcriptional repressor ZEB1. Emerging evidence has indicated that MUC1-C drives a program integrating the induction of EMT with activation of stem cell traits, epigenetic reprogramming and immune evasion...
March 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28301232/molecular-characterization-of-hemorrhagic-enteritis-viruses-hev-detected-in-hev-vaccinated-commercial-turkey-flocks-in-germany
#8
Tamiru Negash Alkie, Ronald Guenther, Silke Rautenschlein
Despite the application of live hemorrhagic enteritis virus (HEV) vaccines, HEV field outbreaks are suspected to still occur in turkey flocks in Germany. Increasing secondary bacterial infections in HEV-vaccinated flocks suggest that vaccines may be losing efficacy or, possibly, that vaccine strains are causing disease. Thus, the goal of the current study was to investigate the diversity of HEV isolates from fattening turkey flocks between 2008 and 2012 by characterizing the open reading frame (ORF)1 gene at its 5' and 3' ends...
March 2017: Avian Diseases
https://www.readbyqxmd.com/read/28292948/focus-issue-cancer-beyond-tumor-genetics-to-protein-landscapes
#9
EDITORIAL
Leslie K Ferrarelli, Nancy R Gough
The proteins that regulate cell proliferation, metastatic potential, survival in circulation, and immune evasion represent most of the targets for therapeutic intervention in cancer. Furthermore, genomic profiling of just the cancer cells leaves critical information about the tumor microenvironment in the dark. The articles highlighted in this Focus Issue describe efforts to translate genomic data into knowledge of aberrant signaling that can be therapeutically targeted and strategies to explore not only the changes that occur in the protein landscape of the tumors but also in the protein profiles of the tumor microenvironment...
March 14, 2017: Science Signaling
https://www.readbyqxmd.com/read/28292946/nox2-dependent-immunosuppression-in-chronic-myelomonocytic-leukemia
#10
Johan Aurelius, Alexander Hallner, Olle Werlenius, Rebecca Riise, Lars Möllgård, Mats Brune, Markus Hansson, Anna Martner, Fredrik B Thorén, Kristoffer Hellstrand
Chronic myelomonocytic leukemia (CMML) is a myeloproliferative and myelodysplastic neoplasm with few treatment options and dismal prognosis. The role of natural killer (NK) cells and other antileukemic lymphocytes in CMML is largely unknown. We aimed to provide insight into the mechanisms of immune evasion in CMML with a focus on immunosuppressive reactive oxygen species (ROS) formed by the myeloid cell NADPH oxidase-2 (NOX2). The dominant population of primary human CMML cells was found to express membrane-bound NOX2 and to release ROS, which, in turn, triggered extensive PARP-1-dependent cell death in cocultured NK cells, CD8(+) T effector memory cells, and CD8(+) T effector cells...
March 14, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28292019/carcinogenesis-mechanisms-of-fusobacterium-nucleatum
#11
REVIEW
Pourya Gholizadeh, Hosein Eslami, Hossein Samadi Kafil
Transformed cells of cancers may be related to stromal cells, immune cells, and some bacteria such as Fusobacterium nucleatum. This review aimed to evaluate carcinogenesis mechanisms of Fusobacterium spp. in the oral cavity, pancreatic and colorectal cancers. These cancers are the three of the ten most prevalence cancer in the worldwide. Recent findings demonstrated that F. nucleatum could be considered as the risk factor for these cancers. The most important carcinogenesis mechanisms of F. nucleatum are chronic infection, interaction of cell surface molecules of these bacteria with immune system and stromal cells, immune evasion and immune suppression...
March 7, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28289089/molecular-pathways-oncologic-pathways-and-their-role-in-t-cell-exclusion-and-immune-evasion-a-new-role-for-the-axl-receptor-tyrosine-kinase
#12
Todd A Aguilera, Amato J Giaccia
With the clinical impact of CTLA-4 and PD-1/PD-L1 immune checkpoint therapies, widespread interest in cancer immunotherapy has been ignited. However, the rate and extent of clinical responses to approved therapies are limited and often non-existent in many solid tumors. This is partially because immune checkpoint therapies are most effective against T-cell inflamed tumors, and non-T-cell inflamed or T-cell excluded tumors remain a significant barrier. New strategies are needed to overcome immune resistance mechanisms that arise during tumor development which result in T-cell exclusion...
March 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28288138/muc1-c-integrates-pd-l1-induction-with-repression-of-immune-effectors-in-non-small-cell-lung-cancer
#13
A Bouillez, H Rajabi, C Jin, M Samur, A Tagde, M Alam, M Hiraki, T Maeda, X Hu, D Adeegbe, S Kharbanda, K-K Wong, D Kufe
Immunotherapeutic approaches, particularly programmed death 1/programmed death ligand 1 (PD-1/PD-L1) blockade, have improved the treatment of non-small-cell lung cancer (NSCLC), supporting the premise that evasion of immune destruction is of importance for NSCLC progression. However, the signals responsible for upregulation of PD-L1 in NSCLC cells and whether they are integrated with the regulation of other immune-related genes are not known. Mucin 1 (MUC1) is aberrantly overexpressed in NSCLC, activates the nuclear factor-κB (NF-κB) p65ZEB1 pathway and confers a poor prognosis...
March 13, 2017: Oncogene
https://www.readbyqxmd.com/read/28287634/immune-microenvironment-of-gliomas
#14
Anna Gieryng, Dominika Pszczolkowska, Kacper A Walentynowicz, Wenson D Rajan, Bozena Kaminska
High-grade gliomas are rapidly progressing tumors of the central nervous system (CNS) with a very poor prognosis despite extensive resection combined with radiation and/or chemotherapy. Histopathological and flow cytometry analyses of human and rodent experimental gliomas revealed heterogeneity of a tumor and its niche, composed of reactive astrocytes, endothelial cells, and numerous immune cells. Infiltrating immune cells consist of CNS resident (microglia) and peripheral macrophages, granulocytes, myeloid-derived suppressor cells (MDSCs), and T lymphocytes...
March 13, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28286708/transcriptomic-analysis-reveals-metabolic-switches-and-surface-remodeling-as-key-processes-for-stage-transition-in-trypanosoma-cruzi
#15
Luisa Berná, Maria Laura Chiribao, Gonzalo Greif, Matias Rodriguez, Fernando Alvarez-Valin, Carlos Robello
American trypanosomiasis is a chronic and endemic disease which affects millions of people. Trypanosoma cruzi, its causative agent, has a life cycle that involves complex morphological and functional transitions, as well as a variety of environmental conditions. This requires a tight regulation of gene expression, which is achieved mainly by post-transcriptional regulation. In this work we conducted an RNAseq analysis of the three major life cycle stages of T. cruzi: amastigotes, epimastigotes and trypomastigotes...
2017: PeerJ
https://www.readbyqxmd.com/read/28284621/identification-of-a-novel-host-specific-igg-protease-in-streptococcus-phocae-subsp-phocae
#16
Viktoria Rungelrath, Jan Christian Wohlsein, Ursula Siebert, Jeffrey Stott, Ellen Prenger-Berninghoff, Ulrich von Pawel-Rammingen, Peter Valentin-Weigand, Christoph G Baums, Jana Seele
Streptococcus (S.) phocae subsp. phocae causes bronchopneumonia and septicemia in a variety of marine mammals. Especially in harbor seals infected with phocine distemper virus it plays an important role as an opportunistic pathogen. This study was initiated by the detection of IgG cleavage products in Western blot analysis after incubation of bacterial supernatant with harbor seal serum. Hence, the objectives of this study were the identification and characterization of a secreted IgG cleaving protease in S...
March 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/28280037/local-activation-of-p53-in-the-tumor-microenvironment-overcomes-immune-suppression-and-enhances-antitumor-immunity
#17
Gang Guo, Miao Yu, Wei Xiao, Esteban Celis, Yan Cui
Mutations in tumor suppressor p53 remain a vital mechanism of tumor escape from apoptosis and senescence. Emerging evidence suggests that p53 dysfunction also fuels inflammation and supports tumor immune evasion, thereby serving as an immunological driver of tumorigenesis. Therefore, targeting p53 in the tumor microenvironment (TME) also represents an immunologically desirable strategy for reversing immunosuppression and enhancing antitumor immunity. Using a pharmacological p53 activator nutlin-3a, we show that local p53 activation in TME comprising overt tumor infiltrating leukocytes (TILeus) induces systemic antitumor immunity and tumor regression, but not in TME with scarce TILeus, such as B16 melanoma...
March 9, 2017: Cancer Research
https://www.readbyqxmd.com/read/28277097/towards-functional-antibody-based-vaccines-to-prevent-pre-erythrocytic-malaria-infection
#18
Brandon Sack, Stefan H I Kappe, D Noah Sather
An effective malaria vaccine would be considered a milestone of modern medicine, yet has so far eluded research and development efforts. This can be attributed to the extreme complexity of the malaria parasites, presenting with a multi-stage life cycle, high genome complexity and the parasite's sophisticated immune evasion measures, particularly antigenic variation during pathogenic blood stage infection. However, the pre-erythrocytic (PE) early infection forms of the parasite exhibit relatively invariant proteomes, and are attractive vaccine targets as they offer multiple points of immune system attack...
March 1, 2017: Expert Review of Vaccines
https://www.readbyqxmd.com/read/28275910/mechanisms-of-drug-resistance-in-melanoma
#19
Matthew Winder, Amaya Virós
Metastatic melanoma is associated with poor outcome and is largely refractory to the historic standard of care. In recent years, the development of targeted small-molecule inhibitors and immunotherapy has revolutionised the care and improved the overall survival of these patients. Therapies targeting BRAF and MEK to block the mitogen-activated protein kinase (MAPK) pathway were the first to show unprecedented clinical responses. Following these encouraging results, antibodies targeting immune checkpoint inhibition molecules cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell death (PD)-1, and PD-ligand1(PD-L1) demonstrated sustained tumour regression in a significant subset of patients by enabling an anti-tumour immunologic response...
March 9, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28275576/the-unique-molecular-and-cellular-microenvironment-of-ovarian-cancer
#20
REVIEW
Thomas Worzfeld, Elke Pogge von Strandmann, Magdalena Huber, Till Adhikary, Uwe Wagner, Silke Reinartz, Rolf Müller
The reciprocal interplay of cancer cells and host cells is an indispensable prerequisite for tumor growth and progression. Cells of both the innate and adaptive immune system, in particular tumor-associated macrophages (TAMs) and T cells, as well as cancer-associated fibroblasts enter into a malicious liaison with tumor cells to create a tumor-promoting and immunosuppressive tumor microenvironment (TME). Ovarian cancer, the most lethal of all gynecological malignancies, is characterized by a unique TME that enables specific and efficient metastatic routes, impairs immune surveillance, and mediates therapy resistance...
2017: Frontiers in Oncology
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