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Immune evasion

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https://www.readbyqxmd.com/read/29777657/mcv-mir-m1-targets-the-host-cell-immune-response-resulting-in-the-attenuation-of-neutrophil-chemotaxis
#1
P Akhbari, D Tobin, K Poterlowicz, W Roberts, J R Boyne
Virus-encoded miRNAs are emerging as key regulators of persistent infection and host-cell immune evasion. Merkel cell polyomavirus (MCPyV), the predominant aetiological agent of Merkel cell carcinoma (MCC), encodes a single miRNA, MCV-miR-M1, which targets the oncogenic MCPyV large T antigen (LT). MCV-miR-M1 has previously been shown to play an important role in establishment of long-term infection, however, the underlying mechanism is not fully understood. A key unanswered question is whether, in addition to auto-regulating LT, MCV-miR-M1 also targets cellular transcripts to orchestrate an environment conducive for persistent infection...
May 16, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29776993/tumor-immune-evasion-arises-through-loss-of-tnf-sensitivity
#2
Conor J Kearney, Stephin J Vervoort, Simon J Hogg, Kelly M Ramsbottom, Andrew J Freeman, Najoua Lalaoui, Lizzy Pijpers, Jessica Michie, Kristin K Brown, Deborah A Knight, Vivien Sutton, Paul A Beavis, Ilia Voskoboinik, Phil K Darcy, John Silke, Joseph A Trapani, Ricky W Johnstone, Jane Oliaro
Immunotherapy has revolutionized outcomes for cancer patients, but the mechanisms of resistance remain poorly defined. We used a series of whole-genome clustered regularly interspaced short palindromic repeat (CRISPR)-based screens performed in vitro and in vivo to identify mechanisms of tumor immune evasion from cytotoxic lymphocytes [CD8+ T cells and natural killer (NK) cells]. Deletion of key genes within the tumor necrosis factor (TNF) signaling, interferon-γ (IFN-γ) signaling, and antigen presentation pathways provided protection of tumor cells from CD8+ T cell-mediated killing and blunted antitumor immune responses in vivo...
May 18, 2018: Science Immunology
https://www.readbyqxmd.com/read/29774068/platelet-camouflaged-nanococktail-simultaneous-inhibition-of-drug-resistant-tumor-growth-and-metastasis-via-a-cancer-cells-and-tumor-vasculature-dual-targeting-strategy
#3
Lijia Jing, Haijing Qu, Dongqi Wu, Chaojian Zhu, Yongbo Yang, Xing Jin, Jian Zheng, Xiangsheng Shi, Xiufeng Yan, Yang Wang
Multidrug resistance (MDR) poses a great challenge to cancer therapy. It is difficult to inhibit the growth of MDR cancer due to its chemoresistance. Furthermore, MDR cancers are more likely to metastasize, causing a high mortality among cancer patients. In this study, a nanomedicine RGD-NPVs@MNPs/DOX was developed by encapsulating melanin nanoparticles (MNPs) and doxorubicin (DOX) inside RGD peptide (c(RGDyC))-modified nanoscale platelet vesicles (RGD-NPVs) to efficiently inhibit the growth and metastasis of drug-resistant tumors via a cancer cells and tumor vasculature dual-targeting strategy...
2018: Theranostics
https://www.readbyqxmd.com/read/29773130/identification-of-emu-tegp11-an-ef-hand-domain-containing-tegumental-protein-of-echinococcus-multilocularis
#4
Yadong Zheng, Xiaola Guo, Meng Su, Xiaoqian Chen, Xiaoliang Jin, Juntao Ding, Zhengrong Wang, Xinwen Bo, Mazhar Ayaz, Ivan Kutyrev, Wanzhong Jia, Xichen Zhang, Jing Zhang
Tegumental proteins (TegPs) are a group of proteins that coat on the surface of worms, mainly being involved in ion uptake and immune evasion. Echinococcus species have many TegPs, but none of them have been characterized and their role remains unclear. The genome-wide analysis revealed that there were at least 14 tegp genes (tegp1 - 14) in Echinococcus species, the majority of which were found to contain an EF-hand domain or a dynein light chain-like domain or both. Despite low identity, all TegP11 proteins from 25 flatworms were conserved in structure...
May 15, 2018: Veterinary Parasitology
https://www.readbyqxmd.com/read/29770278/-2tm-proteins-an-antigenically-diverse-superfamily-with-variable-functions-and-export-pathways
#5
Jasweer Kaur, Rachna Hora
Malaria is a disease that affects millions of people annually. An intracellular habitat and lack of protein synthesizing machinery in erythrocytes pose numerous difficulties for survival of the human pathogen Plasmodium falciparum . The parasite refurbishes the infected red blood cell (iRBC) by synthesis and export of several proteins in an attempt to suffice its metabolic needs and evade the host immune response. Immune evasion is largely mediated by surface display of highly polymorphic protein families known as variable surface antigens...
2018: PeerJ
https://www.readbyqxmd.com/read/29769653/isg15-in-antiviral-immunity-and-beyond
#6
REVIEW
Yi-Chieh Perng, Deborah J Lenschow
The host response to viral infection includes the induction of type I interferons and the subsequent upregulation of hundreds of interferon-stimulated genes. Ubiquitin-like protein ISG15 is an interferon-induced protein that has been implicated as a central player in the host antiviral response. Over the past 15 years, efforts to understand how ISG15 protects the host during infection have revealed that its actions are diverse and pathogen-dependent. In this Review, we describe new insights into how ISG15 directly inhibits viral replication and discuss the recent finding that ISG15 modulates the host damage and repair response, immune response and other host signalling pathways...
May 16, 2018: Nature Reviews. Microbiology
https://www.readbyqxmd.com/read/29768737/providence-of-cd25-kir-cd127-foxp3-cd8-t-cell-subset-determines-the-dynamics-of-tumor-immune-surveillance
#7
Sreeparna Chakraborty, Pushpak Bhattacharjee, Abir K Panda, Kirti Kajal, Sayantan Bose, Gaurisankar Sa
CD8+ T-regulatory cells are progressively emerging as crucial components of immune system. The previous report suggests the presence of FOXP3-positive CD8+ Treg cells, similar to CD4+ Tregs, in cancer patients which produce high levels of IL10 and TGFβ for its immunosuppressive activities. At an early stage of tumor development, we have identified a subset of FOXP3-negative CD8+ CD25+ KIR+ CD127- a Treg-like subset which is essentially IFNγ-positive. However, this early induced CD8+ CD25+ CD127- T cell subset certainly distinct from the IFNγ+ CD8+ T-effecter cells...
May 16, 2018: Immunology and Cell Biology
https://www.readbyqxmd.com/read/29765991/immune-response-and-evasion-mechanisms-of-plasmodium-falciparum-parasites
#8
REVIEW
Esmael Besufikad Belachew
Malaria causes approximately 212 million cases and 429 thousand deaths annually. Plasmodium falciparum is responsible for the vast majority of deaths (99%) than others. The virulence of P. falciparum is mostly associated with immune response-evading ability. It has different mechanisms to evade both Anopheles mosquito and human host immune responses. Immune-evading mechanisms in mosquito depend mainly on the Pfs47 gene that inhibits Janus kinase-mediated activation. Host complement factor also protects human complement immune attack of extracellular gametes in Anopheles mosquito midgut...
2018: Journal of Immunology Research
https://www.readbyqxmd.com/read/29765039/stt3-dependent-pd-l1-accumulation-on-cancer-stem-cells-promotes-immune-evasion
#9
Jung-Mao Hsu, Weiya Xia, Yi-Hsin Hsu, Li-Chuan Chan, Wen-Hsuan Yu, Jong-Ho Cha, Chun-Te Chen, Hsin-Wei Liao, Chu-Wei Kuo, Kay-Hooi Khoo, Jennifer L Hsu, Chia-Wei Li, Seung-Oe Lim, Shih-Shin Chang, Yi-Chun Chen, Guo-Xin Ren, Mien-Chie Hung
Enriched PD-L1 expression in cancer stem-like cells (CSCs) contributes to CSC immune evasion. However, the mechanisms underlying PD-L1 enrichment in CSCs remain unclear. Here, we demonstrate that epithelial-mesenchymal transition (EMT) enriches PD-L1 in CSCs by the EMT/β-catenin/STT3/PD-L1 signaling axis, in which EMT transcriptionally induces N-glycosyltransferase STT3 through β-catenin, and subsequent STT3-dependent PD-L1 N-glycosylation stabilizes and upregulates PD-L1. The axis is also utilized by the general cancer cell population, but it has much more profound effect on CSCs as EMT induces more STT3 in CSCs than in non-CSCs...
May 15, 2018: Nature Communications
https://www.readbyqxmd.com/read/29765020/changes-in-genome-organization-of-parasite-specific-gene-families-during-the-plasmodium-transmission-stages
#10
Evelien M Bunnik, Kate B Cook, Nelle Varoquaux, Gayani Batugedara, Jacques Prudhomme, Anthony Cort, Lirong Shi, Chiara Andolina, Leila S Ross, Declan Brady, David A Fidock, Francois Nosten, Rita Tewari, Photini Sinnis, Ferhat Ay, Jean-Philippe Vert, William Stafford Noble, Karine G Le Roch
The development of malaria parasites throughout their various life cycle stages is coordinated by changes in gene expression. We previously showed that the three-dimensional organization of the Plasmodium falciparum genome is strongly associated with gene expression during its replication cycle inside red blood cells. Here, we analyze genome organization in the P. falciparum and P. vivax transmission stages. Major changes occur in the localization and interactions of genes involved in pathogenesis and immune evasion, host cell invasion, sexual differentiation, and master regulation of gene expression...
May 15, 2018: Nature Communications
https://www.readbyqxmd.com/read/29763438/phasome-analysis-of-pathogenic-and-commensal-neisseria-species-expands-the-known-repertoire-of-phase-variable-genes-and-highlights-common-adaptive-strategies
#11
Joseph J Wanford, Luke R Green, Jack Aidley, Christopher D Bayliss
Pathogenic Neisseria are responsible for significantly higher levels of morbidity and mortality than their commensal relatives despite having similar genetic contents. Neisseria possess a disparate arsenal of surface determinants that facilitate host colonisation and evasion of the immune response during persistent carriage. Adaptation to rapid changes in these hostile host environments is enabled by phase variation (PV) involving high frequency, stochastic switches in expression of surface determinants. In this study, we analysed 89 complete and 79 partial genomes, from the NCBI and Neisseria PubMLST databases, representative of multiple pathogenic and commensal species of Neisseria using PhasomeIt, a new program that identifies putatively phase-variable genes and homology groups by the presence of simple sequence repeats (SSR)...
2018: PloS One
https://www.readbyqxmd.com/read/29762488/high-production-of-lukmf-in-staphylococcus-aureus-field-strains-is-associated-with-clinical-bovine-mastitis
#12
Jurriaan Hoekstra, Victor Rutten, Laura Sommeling, Tine van Werven, Mirlin Spaninks, Birgitta Duim, Lindert Benedictus, Gerrit Koop
Staphylococcus aureus , a major cause of bovine mastitis, produces a wide range of immune-evasion molecules. The bi-component leukocidin LukMF' is a potent killer of bovine neutrophils in vitro. Since the role of LukMF' in development of bovine mastitis has not been studied in natural infections, we aimed to clarify whether presence of the lukM-lukF' genes and production levels of LukMF' are associated with clinical severity of the disease. Staphylococcus aureus was isolated from mastitis milk samples (38 clinical and 17 subclinical cases) from 33 different farms...
May 15, 2018: Toxins
https://www.readbyqxmd.com/read/29762141/pd-1-expression-in-chronic-lymphocytic-leukemia-small-lymphocytic-lymphoma-cll-sll-and-large-b-cell-richter-transformation-dlbcl-rt-a-characteristic-feature-of-dlbcl-rt-and-potential-surrogate-marker-for-clonal-relatedness
#13
Rong He, Wei Ding, David S Viswanatha, Dong Chen, Min Shi, Daniel Van Dyke, Shulan Tian, Linda N Dao, Sameer A Parikh, Tait D Shanafelt, Timothy G Call, Stephen M Ansell, Jose F Leis, Ming Mai, Curtis A Hanson, Karen L Rech
Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is a low-grade B-cell neoplasm and ∼2% to 9% patients develop an aggressive lymphoma, most commonly diffuse large B-cell lymphoma (Richter transformation, DLBCL-RT). Programmed death-1 (PD-1) pathway plays a crucial role in tumor host immunity evasion and its blockade has emerged as an effective anti-cancer immunotherapy. PD-L1 and PD-1 expression has shown predictive value in anti-PD cancer immunotherapy; however, it has not been well documented in CLL/SLL and DLBCL-RT...
May 14, 2018: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29760523/combination-of-fucoidan-based-magnetic-nanoparticles-and-immunomodulators-enhances-tumour-localized-immunotherapy
#14
Chih-Sheng Chiang, Yu-Jung Lin, Rachel Lee, Yen-Ho Lai, Hung-Wei Cheng, Chia-Hung Hsieh, Woei-Cherng Shyu, San-Yuan Chen
Checkpoint immunotherapy that inhibits tumour immune evasion has demonstrated significant clinical success. However, the therapeutic response is limited to certain patient populations, and immunotoxicity as well as autoimmunity have compromised the therapeutic benefits. Here, we report on an inherently therapeutic fucoidan-dextran-based magnetic nanomedicine (IO@FuDex3 ) conjugated with a checkpoint inhibitor (anti-PD-L1) and T-cell activators (anti-CD3 and anti-CD28). IO@FuDex3 can repair the immunosuppressive tumour microenvironment by reinvigorating tumour-infiltrating lymphocytes, while targeting the nanomedicine via magnetic navigation to the tumour to minimize off-target effects...
May 14, 2018: Nature Nanotechnology
https://www.readbyqxmd.com/read/29755477/glycan-shielding-and-modulation-of-hepatitis-c-virus-neutralizing-antibodies
#15
REVIEW
Muriel Lavie, Xavier Hanoulle, Jean Dubuisson
Hepatitis C virus (HCV) envelope glycoprotein heterodimer, E1E2, plays an essential role in virus entry and assembly. Furthermore, due to their exposure at the surface of the virion, these proteins are the major targets of anti-HCV neutralizing antibodies. Their ectodomain are heavily glycosylated with up to 5 sites on E1 and up to 11 sites on E2 modified by N-linked glycans. Thus, one-third of the molecular mass of E1E2 heterodimer corresponds to glycans. Despite the high sequence variability of E1 and E2, N-glycosylation sites of these proteins are generally conserved among the seven major HCV genotypes...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29755471/extracellular-vesicles-shed-by-trypanosoma-cruzi-potentiate-infection-and-elicit-lipid-body-formation-and-pge-2-production-in-murine-macrophages
#16
Maria Isabel Lovo-Martins, Aparecida Donizette Malvezi, Nágela Ghabdan Zanluqui, Bruno Fernando Cruz Lucchetti, Vera Lúcia Hideko Tatakihara, Patricia Alves Mörking, Admilton Gonçalves de Oliveira, Samuel Goldenberg, Pryscilla Fanini Wowk, Phileno Pinge-Filho
During the onset of Trypanosoma cruzi infection, an effective immune response is necessary to control parasite replication and ensure host survival. Macrophages have a central role in innate immunity, acting as an important trypanocidal cell and triggering the adaptive immune response through antigen presentation and cytokine production. However, T. cruzi displays immune evasion mechanisms that allow infection and replication in macrophages, favoring its chronic persistence. One potential mechanism is the release of T...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29755452/influenza-virus-a-master-tactician-in-innate-immune-evasion-and-novel-therapeutic-interventions
#17
REVIEW
Alan Chen-Yu Hsu
Influenza is a contagion that has plagued mankind for many decades, and continues to pose concerns every year, with millions of infections globally. The frequent mutations and recombination of the influenza A virus (IAV) cast a looming threat that antigenically novel strains/subtypes will rise with unpredictable pathogenicity and fear of it evolving into a pandemic strain. There have been four major influenza pandemics, since the beginning of twentieth century, with the great 1918 pandemic being the most severe, killing more than 50 million people worldwide...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29752412/properly-folded-and-functional-porb-from-neisseria-gonorrhoeae-inhibits-dendritic-cell-stimulation-of-cd4-t-cell-proliferation
#18
Weiyan Zhu, Joshua Tomberg, Kayla J Knilans, James E Anderson, Karen P McKinnon, Gregory D Sempowski, Robert A Nicholas, Joseph A Duncan
Neisseria gonorrhoeae is an exclusive human pathogen that evades the host immune system through multiple mechanisms. We have shown that N. gonorrhoeae  suppresses the capacity of antigen-presenting cells to induce CD4+ T cell proliferation. In this study, we sought to determine the gonococcal factors involved in this adaptive immune suppression. We show that suppression of the capacity of antigen-pulsed dendritic cells to induce T cell proliferation is recapitulated by administration of a high molecular weight fraction of conditioned medium from N...
May 11, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29751789/mechanisms-of-immune-evasion-in-breast-cancer
#19
Joshua P Bates, Roshanak Derakhshandeh, Laundette Jones, Tonya J Webb
Tumors develop multiple mechanisms of immune evasion as they progress, with some cancer types being inherently better at 'hiding' than others. With an increased understanding of tumor immune surveillance, immunotherapy has emerged as a promising treatment strategy for breast cancer, despite historically being thought of as an immunologically silent neoplasm. Some types of cancer, such as melanoma, bladder, and renal cell carcinoma, have demonstrated a durable response to immunotherapeutic intervention, however, breast neoplasms have not shown the same efficacy...
May 11, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29749010/borrelia-burgdorferi-surface-located-lmp1-protein-processed-into-region-specific-polypeptides-that-are-critical-for-microbial-persistence
#20
Xuran Zhuang, Xiuli Yang, Amanda S Altieri, Daniel C Nelson, Utpal Pal
One of the Borrelia burgdorferi virulence determinants, annotated as Lmp1, is a surface-exposed, conserved and potential multi-domain protein involved in various functions in spirochete infectivity. Lmp1 contributes to host-pathogen interactions and evasion of host adaptive immunity by spirochetes. Here we show that in diverse B. burgdorferi species, Lmp1 exists as distinct, region-specific and lower molecular mass polypeptides encompassing one or more domains, including independent N-terminal and middle regions and a combined middle and C-terminal region...
May 10, 2018: Cellular Microbiology
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