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Immune evasion

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https://www.readbyqxmd.com/read/29330469/mycobacterium-tuberculosis-exploits-a-molecular-off-switch-of-the-immune-system-for-intracellular-survival
#1
Ulrich von Both, Maurice Berk, Paul-Michael Agapow, Joseph D Wright, Anna Git, Melissa Shea Hamilton, Greg Goldgof, Nazneen Siddiqui, Evangelos Bellos, Victoria J Wright, Lachlan J Coin, Sandra M Newton, Michael Levin
Mycobacterium tuberculosis (M. tuberculosis) survives and multiplies inside human macrophages by subversion of immune mechanisms. Although these immune evasion strategies are well characterised functionally, the underlying molecular mechanisms are poorly understood. Here we show that during infection of human whole blood with M. tuberculosis, host gene transcriptional suppression, rather than activation, is the predominant response. Spatial, temporal and functional characterisation of repressed genes revealed their involvement in pathogen sensing and phagocytosis, degradation within the phagolysosome and antigen processing and presentation...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29328436/role-of-exosomes-and-exosomal-micrornas-in-hepatocellular-carcinoma-potential-in-diagnosis-and-antitumour-treatments-review
#2
Jing-Hua Pan, Hong Zhou, Xiao-Xu Zhao, Hui Ding, Wei Li, Li Qin, Yun-Long Pan
Communication between hepatocellular carcinoma (HCC) cells and their environment is essential for the development and progression of HCC. Exosomes, which are microvesicles secreted by a number of cell types, are carriers of intercellular information and regulate the tumour microenvironment. Studies have demonstrated that exosomes are involved in the communication between HCC cells, endothelial cells and stem cells, and that they serve important roles in the metastasis and invasion, immune evasion and immunotherapy of HCC...
January 11, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29326431/impact-of-oncogenic-pathways-on-evasion-of-antitumour-immune-responses
#3
REVIEW
Stefani Spranger, Thomas F Gajewski
Immunotherapeutic interventions are showing effectiveness across a wide range of cancer types, but only a subset of patients shows clinical response to therapy. Responsiveness to checkpoint blockade immunotherapy is favoured by the presence of a local, CD8+ T cell-based immune response within the tumour microenvironment. As molecular analyses of tumours containing or lacking a productive CD8+ T cell infiltrate are being pursued, increasing evidence is indicating that activation of oncogenic pathways in tumour cells can impair induction or execution of a local antitumour immune response...
January 12, 2018: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/29325778/nonstructural-proteins-nsp2tf-and-nsp2n-of-porcine-reproductive-and-respiratory-syndrome-virus-prrsv-play-important-roles-in-suppressing-host-innate-immune-responses
#4
Y Li, P Shang, D Shyu, C Carrillo, P Naraghi-Arani, Crystal J Jaing, G J Renukaradhya, A E Firth, E J Snijder, Y Fang
Recently, we identified a unique -2/-1 ribosomal frameshift mechanism in PRRSV, which yields two truncated forms of nonstructural protein (nsp) 2 variants, nsp2TF and nsp2N. Here, in vitro expression of individual PRRSV nsp2TF and nsp2N demonstrated their ability to suppress cellular innate immune responses in transfected cells. Two recombinant viruses were further analyzed, in which either nsp2TF was C-terminally truncated (vKO1) or expression of both nsp2TF and nsp2N was knocked out (vKO2). Host cellular mRNA profiling showed that a panel of cellular immune genes, in particular those involved in innate immunity, was upregulated in cells infected with vKO1 and vKO2...
January 8, 2018: Virology
https://www.readbyqxmd.com/read/29324974/the-role-of-endoplasmic-reticulum-aminopeptidase-2-erap2-in-modulating-immune-detection-of-choriocarcinoma
#5
Michelle D Warthan, Sonya L Washington, Samone E Franzese, Ronald M Ramus, Kyu-Rae Kim, Timothy P York, Efstratios Stratikos, Jerome F Strauss, Eun D Lee
Gestational choriocarcinomas are derived from placental trophoblast cells, with HLA-C being the only class I polymorphic molecule expressed. However, choriocarcinomas have not been profiled for endoplasmic reticulum aminopeptidase 2 (ERAP2) expression. ERAP2 trims peptides presented by human leukocyte antigens (HLA) have shown to modulate immune response. Over 50% of choriocacinomas we screened lack ERAP2 expression, which suggests the absence of ERAP2 expression allows immune evasion of choriocarcinoma cells...
January 9, 2018: Biology of Reproduction
https://www.readbyqxmd.com/read/29321322/dengue-virus-selectively-annexes-endoplasmic-reticulum-associated-translation-machinery-as-a-strategy-for-co-opting-host-cell-protein-synthesis
#6
David W Reid, Rafael K Campos, Jessica R Child, Tianli Zheng, Kitti Wing Ki Chan, Shelton S Bradrick, Subhash G Vasudevan, Mariano A Garcia-Blanco, Christopher V Nicchitta
A primary question in Dengue virus (DENV) biology is the molecular strategy for recruitment of host cell protein synthesis machinery. Here we combined cell fractionation, ribosome profiling, and RNA-seq to investigate the subcellular organization of viral genome translation and replication as well as host cell translation and its response to DENV infection. We report that throughout the viral life cycle, DENV (+) and (-) strand RNAs were highly partitioned to the endoplasmic reticulum (ER), identifying the ER as the primary site of DENV translation...
January 10, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29321314/hla-class-i-downregulation-by-hiv-1-variants-from-subtype-c-transmission-pairs
#7
Zachary Ende, Martin J Deymier, Daniel T Claiborne, Jessica L Prince, Daniela C Mónaco, William Kilembe, Susan A Allen, Eric Hunter
HIV-1 downregulates HLA-A and HLA-B from the surface of infected cells primarily to evade CD8 T cell recognition. HLA-C was thought to remain on the cell surface and bind inhibitory killer immunoglobulin-like receptors, preventing NK cell-mediated suppression. However, a recent study found HIV-1 primary viruses have the capacity to downregulate HLA-C. The goal of this study was to assess the heterogeneity of HLA-A, HLA-B and HLA-C downregulation among full-length primary viruses from six chronically infected and six newly infected individuals from transmission pairs, and to determine whether transmitted/founder variants exhibit common HLA class I downregulation characteristics...
January 10, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29321187/infection-by-the-helminth-parasite-fasciola-hepatica-requires-rapid-regulation-of-metabolic-virulence-and-invasive-factors-to-adjust-to-its-mammalian-host
#8
Krystyna Cwiklinski, Heather Jewhurst, Paul McVeigh, Tara Barbour, Aaron G Maule, Jose Tort, Sandra M O'Neill, Mark W Robinson, Sheila Donnelly, John P Dalton
The parasite Fasciola hepatica infects a broad range of mammals with impunity.  Following ingestion of parasites (metacercariae) by the host, newly excysted juveniles (NEJ) emerge from their cysts, rapidly penetrate the duodenal wall and migrate to the liver.  Successful infection takes just a few hours and involves negotiating hurdles presented by host macromolecules, tissues and micro-environments, as well as the immune system.  Here, transcriptome and proteome analysis of ex vivo F. hepatica metacercariae and NEJ reveal the rapidity and multitude of metabolic and developmental alterations that take place in order for the parasite to establish infection...
January 10, 2018: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29319806/comparative-genomics-highlights-symbiotic-capacities-and-high-metabolic-flexibility-of-the-marine-genus-pseudovibrio
#9
Dennis Versluis, Bart Nijsse, Mohd Azrul Naim, Jasper J Koehorst, Jutta Wiese, Johannes F Imhoff, Peter J Schaap, Mark W J van Passel, Hauke Smidt, Detmer Sipkema
Pseudovibrio is a marine bacterial genus members of which are predominantly isolated from sessile marine animals, and particularly sponges. It has been hypothesised that Pseudovibrio spp. form mutualistic relationships with their hosts. Here, we studied Pseudovibrio phylogeny and genetic adaptations that may play a role in host colonization by comparative genomics of 31 Pseudovibrio strains, including 25 sponge isolates. All genomes were highly similar in terms of encoded core metabolic pathways, albeit with substantial differences in overall gene content...
January 8, 2018: Genome Biology and Evolution
https://www.readbyqxmd.com/read/29319233/genetic-evolution-of-classical-swine-fever-virus-under-immune-environments-conditioned-by-genotype-1-based-modified-live-virus-vaccine
#10
S J Yoo, T Kwon, K Kang, H Kim, S C Kang, J A Richt, Y S Lyoo
Modified live vaccines (MLVs) based on genotype 1 strains, particularly C-strain, have been used to prevent and control classical swine fever virus (CSFV) worldwide. Nevertheless, a shift in the predominant CSFV strains circulating in the field from genotype 1 or 3 to genotype 2 is seen. Genotype 2 is genetically distant from the vaccine strains and was recently reported during outbreaks after vaccine failure; this has raised concerns that vaccination has influenced viral evolution. In Korea in 2016, there was an unexpected CSF outbreak in a MLV-vaccinated commercial pig herd...
January 10, 2018: Transboundary and Emerging Diseases
https://www.readbyqxmd.com/read/29318591/immune-checkpoint-molecules-in-acute-myeloid-leukaemia-managing-the-double-edged-sword
#11
REVIEW
Willemijn Hobo, Tim J A Hutten, Nicolaas P M Schaap, Harry Dolstra
New immunotherapeutic interventions have revolutionized cancer treatment. The immune responsiveness of acute myeloid leukaemia (AML) was first demonstrated by allogeneic stem cell transplantation. In addition, milder immunotherapeutic approaches are exploited. However, the long-term efficacy of these therapies is hampered by various immune resistance and editing mechanisms. In this regard, co-inhibitory signalling pathways have been shown to play a crucial role. Via up-regulation of inhibitory checkpoints, tumour-reactive T cell and Natural Killer cell responses can be strongly impeded...
January 9, 2018: British Journal of Haematology
https://www.readbyqxmd.com/read/29317664/human-cytomegalovirus-encoded-us9-targets-mavs-and-sting-signaling-to-evade-type-i-interferon-immune-responses
#12
Hyun Jin Choi, Areum Park, Sujin Kang, Eunhye Lee, Taeyun A Lee, Eun A Ra, Jiseon Lee, Sungwook Lee, Boyoun Park
Human cytomegalovirus (HCMV) has evolved sophisticated immune evasion mechanisms that target both the innate and adaptive immune responses. However, how HCMV encoded proteins are involved in this immune escape is not clear. Here, we show that HCMV glycoprotein US9 inhibits the IFN-β response by targeting the mitochondrial antiviral-signaling protein (MAVS) and stimulator of interferon genes (STING)-mediated signaling pathways. US9 accumulation in mitochondria attenuates the mitochondrial membrane potential, leading to promotion of MAVS leakage from the mitochondria...
January 9, 2018: Nature Communications
https://www.readbyqxmd.com/read/29317280/post-diagnosis-aspirin-use-and-overall-survival-in-patients-with-melanoma
#13
Saleh Rachidi, Kristin Wallace, Hong Li, Tim Lautenschlaeger, Zihai Li
BACKGROUND: Mouse studies show that tumor-derived prostaglandins and platelets promote melanoma progression and immune-evasion. OBJECTIVE: Determine if aspirin confers longer survival in patients with melanoma. METHSODS: A retrospective cohort study of 1,522 patients at Indiana University Health (IUH) diagnosed with melanoma between 2000 and 2014 and followed up through September, 2016. RESULTS: Aspirin use was associated with longer overall survival in univariate analysis and after controlling for age, sex, stage, and treatment modalities (HR 0...
January 6, 2018: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/29315015/tumor-specific-t-cells-engineered-to-overcome-tumor-immune-evasion-induce-clinical-responses-in-patients-with-relapsed-hodgkin-lymphoma
#14
Catherine M Bollard, Tamara Tripic, Conrad Russell Cruz, Gianpietro Dotti, Stephen Gottschalk, Vicky Torrano, Olga Dakhova, George Carrum, Carlos A Ramos, Hao Liu, Meng-Fen Wu, Andrea N Marcogliese, Cecilia Barese, Youli Zu, Daniel Y Lee, Owen O'Connor, Adrian P Gee, Malcolm K Brenner, Helen E Heslop, Cliona M Rooney
Purpose Transforming growth factor-β (TGF-β) production in the tumor microenvironment is a potent and ubiquitous tumor immune evasion mechanism that inhibits the expansion and function of tumor-directed responses; therefore, we conducted a clinical study to discover the effects of the forced expression of a dominant-negative TGF-β receptor type 2 (DNRII) on the safety, survival, and activity of infused tumor-directed T cells. Materials and Methods In a dose escalation study, eight patients with Epstein Barr virus-positive Hodgkin lymphoma received two to 12 doses of between 2 × 107 and 1...
January 9, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29309569/targeting-sialic-acid-siglec-interactions-to-reverse-immune-suppression-in-cancer
#15
Olivia Joan Adams, Michal A Stanczak, Stephan von Gunten, Heinz Läubli
Changes in sialic acids in cancer have been observed for many years. In particular, the increase of sialoglycan density or hypersialylation in tumors has been described. Recent studies have identified mechanisms for immune evasion based on sialoglycan interactions with immunoregulatory Siglec receptors that are exploited by tumor cells and microorganisms alike. Siglecs are mostly inhibitory receptors similar to known immune checkpoints including PD-1 or CTLA-4 that are successfully targeted with blocking antibodies for cancer immunotherapy...
December 22, 2017: Glycobiology
https://www.readbyqxmd.com/read/29308328/b-cell-lymphoma-progression-promotes-the-accumulation-of-circulating-ly6clo-monocytes-with-immunosuppressive-activity
#16
Sara J McKee, Zewen K Tuong, Takumi Kobayashi, Brianna L Doff, Megan Sf Soon, Michael Nissen, Pui Yeng Lam, Colm Keane, Frank Vari, Davide Moi, Roberta Mazzieri, Graham Leggatt, Maher K Gandhi, Stephen R Mattarollo
Monocytosis is considered a poor prognostic factor for many cancers, including B cell lymphomas. The mechanisms by which different monocyte subsets support the growth of lymphoma is poorly understood. Using a pre-clinical mouse model of B cell non-Hodgkin's lymphoma (B-NHL), we investigated the impact of tumor progression on circulating monocyte levels, subset distribution and their activity, with a focus on immune suppression. B-NHL development corresponded with significant expansion initially of classical (Ly6Chi) and non-classical (Ly6Clo) monocytes, with accumulation and eventual predominance of Ly6Clo cells...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29308322/impaired-nk-cell-recognition-of-vemurafenib-treated-melanoma-cells-is-overcome-by-simultaneous-application-of-histone-deacetylase-inhibitors
#17
Sheila López-Cobo, Natalia Pieper, Carmen Campos-Silva, Eva M García-Cuesta, Hugh T Reyburn, Annette Paschen, Mar Valés-Gómez
Therapy of metastatic melanoma advanced recently with the clinical implementation of signalling pathway inhibitors, such as vemurafenib, specifically targeting mutant BRAFV600E. In general, patients experience remarkable clinical responses under BRAF inhibitor (BRAFi) treatment but eventually progress within 6-8 months due to resistance development. Responding metastases show an increased immune cell infiltrate, including also NK cells, that, however, is no longer detectable in BRAFi-resistant lesions, suggesting NK cell activity should be exploited to prevent disease progression...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29308317/high-numbers-of-pdcd1-pd-1-positive-t-cells-and-b2m-mutations-in-microsatellite-unstable-colorectal-cancer
#18
Jonas Janikovits, Meike Müller, Julia Krzykalla, Sandrina Körner, Fabian Echterdiek, Bernd Lahrmann, Niels Grabe, Martin Schneider, Axel Benner, Magnus von Knebel Doeberitz, Matthias Kloor
DNA mismatch repair (MMR)-deficient cancers accumulate high numbers of coding microsatellite mutations, which lead to the generation of highly immunogenic frameshift peptide (FSP) neoantigens. MMR-deficient cells can grow out to clinically manifest cancers either if they evade immune cell attack or if local T-cells get exhausted. Therefore, a subset of MSI cancer patients responds particularly well to treatment with immune checkpoint inhibitors. We analyzed whether immune evasion in MMR-deficient cancer mediated by loss of HLA class I or II antigens is related to local immune cell activation status...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29308299/platelet-mediated-shedding-of-nkg2d-ligands-impairs-nk-cell-immune-surveillance-of-tumor-cells
#19
Stefanie Maurer, Korbinian Nepomuk Kropp, Gerd Klein, Alexander Steinle, Sebastian P Haen, Juliane S Walz, Clemens Hinterleitner, Melanie Märklin, Hans-Georg Kopp, Helmut Rainer Salih
Platelets promote metastasis, among others by coating cancer cells traveling through the blood, which results in protection from NK cell immune-surveillance. The underlying mechanisms, however, remain to be fully elucidated. Here we report that platelet-coating reduces surface expression of NKG2D ligands, in particular MICA and MICB, on tumor cells, which was mirrored by enhanced release of their soluble ectodomains. Similar results were obtained upon exposure of tumor cells to platelet-releasate and can be attributed to the sheddases ADAM10 and ADAM17 that are detectable on the platelet surface and in releasate following activation and at higher levels on platelets of patients with metastasized lung cancer compared with healthy controls...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29306874/a-structurally-dynamic-n-terminal-region-drives-function-of-the-staphylococcal-peroxidase-inhibitor-spin
#20
Nienke W M de Jong, Nicoleta T Ploscariu, Kasra X Ramyar, Brandon L Garcia, Alvaro I Herrera, Om Prakash, Benjamin B Katz, Kevin G Leidal, William Nauseef, Kok van Kessel, Jos van Strijp, Brian V Geisbrecht
The heme-containing enzyme myeloperoxidase (MPO) is critical for optimal antimicrobial activity of human neutrophils. We recently discovered that the bacterium Staphylococcus aureus expresses a novel immune evasion protein, called SPIN, that binds tightly to MPO, inhibits MPO activity, and contributes to bacterial survival following phagocytosis. A co-crystal structure of SPIN bound to MPO suggested that SPIN blocks substrate access to the catalytic heme by inserting an N-terminal β-hairpin into the MPO active site channel...
January 5, 2018: Journal of Biological Chemistry
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