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Immunoevasion

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https://www.readbyqxmd.com/read/27814389/correction-influenza-virus-targets-class-i-mhc-educated-nk-cells-for-immunoevasion
#1
Ahmad Bakur Mahmoud, Megan M Tu, Andrew Wight, Haggag S Zein, Mir Munir A Rahim, Seung-Hwan Lee, Harman S Sekhon, Earl G Brown, Andrew P Makrigiannis
[This corrects the article DOI: 10.1371/journal.ppat.1005446.].
November 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27795425/recombinant-receptor-binding-domains-of-multiple-mers-coronaviruses-induce-cross-neutralizing-antibodies-against-divergent-human-and-camel-mers-coronaviruses-and-antibody-escape-mutants
#2
Wanbo Tai, Yufei Wang, Craig A Fett, Guangyu Zhao, Fang Li, Stanley Perlman, Shibo Jiang, Yusen Zhou, Lanying Du
: Middle East respiratory syndrome coronavirus (MERS-CoV) binds to cellular receptor dipeptidyl peptidase 4 (DPP4) via spike (S) protein receptor-binding domain (RBD). The RBD contains critical neutralizing epitopes and serves as an important vaccine target. Since RBD mutations occur in different MERS-CoV isolates and antibody-escape mutants, cross-neutralization of divergent MERS-CoV strains by RBD-induced antibodies remains unknown. Here, we constructed four recombinant RBD (rRBD) proteins with single or multiple mutations detected in representative human MERS-CoV strains from the 2012, 2013, 2014 and 2015 outbreaks, respectively, and one rRBD protein with multiple changes derived from camel MERS-CoV strains...
October 19, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27642757/costimulatory-effects-of-an-immunodominant-parasite-antigen-paradoxically-prevent-induction-of-optimal-cd8-t-cell-protective-immunity
#3
Christopher S Eickhoff, Xiuli Zhang, Jose R Vasconcelos, R Geoffrey Motz, Nicole L Sullivan, Kelly O'Shea, Nicola Pozzi, David W Gohara, Jennifer R Blase, Enrico Di Cera, Daniel F Hoft
Trypanosoma cruzi infection is controlled but not eliminated by host immunity. The T. cruzi trans-sialidase (TS) gene superfamily encodes immunodominant protective antigens, but expression of altered peptide ligands by different TS genes has been hypothesized to promote immunoevasion. We molecularly defined TS epitopes to determine their importance for protection versus parasite persistence. Peptide-pulsed dendritic cell vaccination experiments demonstrated that one pair of immunodominant CD4+ and CD8+ TS peptides alone can induce protective immunity (100% survival post-lethal parasite challenge)...
September 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27550523/identification-and-characterization-of-complex-glycosylated-peptides-presented-by-the-mhc-class-ii-processing-pathway-in-melanoma
#4
Stacy Alyse Malaker, Michael J Ferracane, Florence R Depontieu, Angela L Zarling, Jeffrey Shabanowitz, Dina L Bai, Suzanne L Topalian, Victor H Engelhard, Donald F Hunt
The MHC class II processing pathway presents peptides derived from exogenous or membrane-bound proteins to CD4+ T cells. Several studies have shown that glycopeptides are necessary to modulate CD4+ T cell recognition, though glycopeptide structures in these cases are generally unknown. Here we present a total of 93 glycopeptides from three melanoma cell lines and one matched EBV-transformed line, with most found only in the melanoma cell lines. The glycosylation we detected was diverse and comprised 17 different glycoforms...
August 22, 2016: Journal of Proteome Research
https://www.readbyqxmd.com/read/27545071/outrunning-the-red-queen-bystander-activation-as-a-means-of-outpacing-innate-immune-subversion-by-intracellular-pathogens
#5
Alicia M Holmgren, Cameron A McConkey, Sunny Shin
Originally described by the late evolutionary biologist Leigh Van Valen, the Red Queen hypothesis posits that the evolutionary arms race between hosts and their pathogens selects for discrete, genetically encoded events that lead to competitive advantages over the other species. Examples of immune evasion strategies are seen throughout the co-evolution of the mammalian immune system and pathogens, such as the enzymatic inactivation of nuclear factor-κB signaling or host translation by pathogen-encoded virulence factors...
August 22, 2016: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/27535621/spatially-selective-depletion-of-tumor-associated-regulatory-t-cells-with-near-infrared-photoimmunotherapy
#6
Kazuhide Sato, Noriko Sato, Biying Xu, Yuko Nakamura, Tadanobu Nagaya, Peter L Choyke, Yoshinori Hasegawa, Hisataka Kobayashi
Current immunotherapies for cancer seek to modulate the balance among different immune cell populations, thereby promoting antitumor immune responses. However, because these are systemic therapies, they often cause treatment-limiting autoimmune adverse effects. It would be ideal to manipulate the balance between suppressor and effector cells within the tumor without disturbing homeostasis elsewhere in the body. CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) are well-known immunosuppressor cells that play a key role in tumor immunoevasion and have been the target of systemic immunotherapies...
August 17, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27493076/advanced-age-negatively-impacts-survival-in-an-experimental-brain-tumor-model
#7
Erik Ladomersky, Lijie Zhai, Galina Gritsina, Matthew Genet, Kristen L Lauing, Meijing Wu, C David James, Derek A Wainwright
Glioblastoma (GBM) is the most common primary malignant brain tumor in adults, with an average age of 64 years at the time of diagnosis. To study GBM, a number of mouse brain tumor models have been utilized. In these animal models, subjects tend to range from 6 to 12 weeks of age, which is analogous to that of a human teenager. Here, we examined the impact of age on host immunity and the gene expression associated with immune evasion in immunocompetent mice engrafted with syngeneic intracranial GL261. The data indicate that, in mice with brain tumors, youth conveys an advantage to survival...
September 6, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/27217833/safe-and-immunocompatible-nanocarriers-cloaked-in-rbc-membranes-for-drug-delivery-to-treat-solid-tumors
#8
Brian T Luk, Ronnie H Fang, Che-Ming J Hu, Jonathan A Copp, Soracha Thamphiwatana, Diana Dehaini, Weiwei Gao, Kang Zhang, Shulin Li, Liangfang Zhang
The therapeutic potential of nanoparticle-based drug carriers depends largely on their ability to evade the host immune system while delivering their cargo safely to the site of action. Of particular interest are simple strategies for the functionalization of nanoparticle surfaces that are both inherently safe and can also bestow immunoevasive properties, allowing for extended blood circulation times. Here, we evaluated a recently reported cell membrane-coated nanoparticle platform as a drug delivery vehicle for the treatment of a murine model of lymphoma...
2016: Theranostics
https://www.readbyqxmd.com/read/27199990/licensed-and-unlicensed-nk-cells-differential-roles-in-cancer-and-viral-control
#9
REVIEW
Megan M Tu, Ahmad Bakur Mahmoud, Andrew P Makrigiannis
Natural killer (NK) cells are known for their well characterized ability to control viral infections and eliminate tumor cells. Through their repertoire of activating and inhibitory receptors, NK cells are able to survey different potential target cells for various surface markers, such as MHC-I - which signals to the NK cell that the target is healthy - as well as stress ligands or viral proteins, which alert the NK cell to the aberrant state of the target and initiate a response. According to the "licensing" hypothesis, interactions between self-specific MHC-I receptors - Ly49 in mice and KIR in humans - and self-MHC-I molecules during NK cell development is crucial for NK cell functionality...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27156518/the-inhibition-of-cysteine-proteases-rhodesain-and-tbcatb-a-valuable-approach-to-treat-human-african-trypanosomiasis
#10
Roberta Ettari, Santo Previti, Lucia Tamborini, Gregorio Cullia, Silvana Grasso, Maria Zappalà
Human African Trypanosomiasis (HAT) is an endemic parasitic disease of sub-Saharan Africa, caused by two subspecies of protozoa belonging to Trypanosoma genus: T. brucei gambiense and T. brucei rhodesiense. In this context the inhibition of the papain-family cysteine proteases rhodesain and TbCatB has to be considered a promising strategy for HAT treatment. Rhodesain, the major cathepsin L-like cysteine protease of T. brucei rhodesiense, is a lysosomal protease essential for parasite survival. It is involved in parasite invasivity, allowing it to cross the blood-brain barrier (BBB) of the human host, causing the second lethal stage of the disease...
2016: Mini Reviews in Medicinal Chemistry
https://www.readbyqxmd.com/read/27072237/dendritic-cell-vaccination-enhances-antiangiogenesis-induced-by-endostatin-in-rat-glioma
#11
Xia Zhou, Yiwei Liao, Haoyu Li, Zijin Zhao, Qing Liu
CONTEXT: It has been verified that dendritic cell (DC) vaccination can improve the prognosis of malignant glioma. However, recent evidence suggests the problems with DC vaccines lies, at least in part, with the cancers ability to induce an immunosupressive response that suppresses any vaccine-mediated active immunity. Our previous studies indicate that subcutaneous vaccine can restrain the cancer cells implanted in the brain, but the effect is limited on vascularized tumor in the brain...
January 2016: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/26998085/expression-of-the-galectin-9-tim-3-pathway-in-glioma-tissues-is-associated-with-the-clinical-manifestations-of-glioma
#12
Zengjin Liu, Huamin Han, Xin He, Shouwei Li, Chenxing Wu, Chunjiang Yu, Shengdian Wang
Glioma is known to induce local and systemic immunosuppression, which inhibits antitumor T cell responses. The galectin-9-Tim-3-pathway negatively regulates T cell pathways in the tumor immunosuppressive environment. The present study assessed the expression of Tim-3 and galectin-9 in glioma patients, and evaluated the association between the expression of Tim-3 and galectin-9 with clinical characteristics. The present study identified that Tim-3 expression was significantly increased in peripheral blood T cells of glioma patients compared with those of healthy controls, and was additionally increased on tumor-infiltrating T cells...
March 2016: Oncology Letters
https://www.readbyqxmd.com/read/26928844/influenza-virus-targets-class-i-mhc-educated-nk-cells-for-immunoevasion
#13
Ahmad Bakur Mahmoud, Megan M Tu, Andrew Wight, Haggag S Zein, Mir Munir A Rahim, Seung-Hwan Lee, Harman S Sekhon, Earl G Brown, Andrew P Makrigiannis
The immune response to influenza virus infection comprises both innate and adaptive defenses. NK cells play an early role in the destruction of tumors and virally-infected cells. NK cells express a variety of inhibitory receptors, including those of the Ly49 family, which are functional homologs of human killer-cell immunoglobulin-like receptors (KIR). Like human KIR, Ly49 receptors inhibit NK cell-mediated lysis by binding to major histocompatibility complex class I (MHC-I) molecules that are expressed on normal cells...
February 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/26913599/the-mir-27a-calreticulin-axis-affects-drug-induced-immunogenic-cell-death-in-human-colorectal-cancer-cells
#14
T Colangelo, G Polcaro, P Ziccardi, L Muccillo, M Galgani, B Pucci, M Rita Milone, A Budillon, M Santopaolo, G Mazzoccoli, G Matarese, L Sabatino, V Colantuoni
Immunogenic cell death (ICD) evoked by chemotherapeutic agents implies emission of selected damage-associated molecular patterns (DAMP) such as cell surface exposure of calreticulin, secretion of ATP and HMGB1. We sought to verify whether miR-27a is implicated in ICD, having demonstrated that it directly targets calreticulin. To this goal, we exposed colorectal cancer cell lines, genetically modified to express high or low miR-27a levels, to two bona fide ICD inducers (mitoxantrone and oxaliplatin). Low miR-27a-expressing cells displayed more ecto-calreticulin on the cell surface and increased ATP and HMGB1 secretion than high miR-27a-expressing ones in time-course experiments upon drug exposure...
2016: Cell Death & Disease
https://www.readbyqxmd.com/read/26855039/middle-east-respiratory-syndrome-and-severe-acute-respiratory-syndrome
#15
REVIEW
Rahul Vijay, Stanley Perlman
The recent emergence of the Middle East respiratory syndrome (MERS)-CoV, a close relative of the Severe Acute respiratory syndrome (SARS)-CoV, both of which caused a lethal respiratory infection in humans, reinforces the need for further understanding of coronavirus pathogenesis and the host immune response. These viruses have evolved diverse strategies to evade and block host immune responses, facilitating infection and transmission. Pathogenesis following infection with these viruses is characterized by a marked delay in the induction of Type I interferon (IFN I) and, subsequently, by a poor adaptive immune response...
February 2016: Current Opinion in Virology
https://www.readbyqxmd.com/read/26502318/wall-teichoic-acids-prevent-antibody-binding-to-epitopes-within-the-cell-wall-of-staphylococcus-aureus
#16
Samir Gautam, Taehan Kim, Evan Lester, Deeksha Deep, David A Spiegel
Staphylococcus aureus is a Gram-positive bacterial pathogen that produces a range of infections including cellulitis, pneumonia, and septicemia. The principle mechanism in antistaphylococcal host defense is opsonization with antibodies and complement proteins, followed by phagocytic clearance. Here we use a previously developed technique for installing chemical epitopes in the peptidoglycan cell wall to show that surface glycopolymers known as wall teichoic acids conceal cell wall epitopes, preventing their recognition and opsonization by antibodies...
January 15, 2016: ACS Chemical Biology
https://www.readbyqxmd.com/read/26405597/thioredoxin-induces-tregs-to-generate-an-immunotolerant-tumor-microenvironment-in-metastatic-melanoma
#17
Xiaogang Wang, Haisheng Dong, Qi Li, Yingxian Li, An Hong
Metastatic melanoma is a highly aggressive cancer that is very difficult to treat. Additionally, the antitumor immune reaction of melanoma is still unclear. Here we demonstrate an association between the expression and secretion of the antioxidant protein thioredoxin (TRX) and increasing tumor stage and metastasis in melanoma. To elucidate the role of TRX in melanoma, we assessed the correlation of TRX expression with different disease parameters in melanoma. We also examined the in vitro and in vivo effects of modulating TRX levels in melanoma cells using various methods of TRX depletion and augmentation...
September 2015: Oncoimmunology
https://www.readbyqxmd.com/read/26284927/b7h1-expression-and-epithelial-to-mesenchymal-transition-phenotypes-on-colorectal-cancer-stem-like-cells
#18
Yidan Zhi, Zhirong Mou, Jun Chen, Yujun He, Hui Dong, Xiaolan Fu, Yuzhang Wu
Cancer stem cells (CSCs) can invade and metastasize by epithelial-to-mesenchymal transition (EMT). However, how they escape immune surveillance is unclear. B7H1 is crucial negative co-stimulatory molecule but little information about whether it works in CSCs. Therefore, we determined the expression of B7H1 and EMT-associated markers in colorectal cancer stem-like cells to investigate a possible immunoevasion way of CSCs. We enriched CD133+ colorectal cancer cells which manifested the CSCs-like properties such as higher levels of other stem cell markers Oct-4 and Sox-2, tumor sphere forming ability and more tumorigenic in NOD/SCID mice...
2015: PloS One
https://www.readbyqxmd.com/read/26215614/a-biphasic-epigenetic-switch-controls-immunoevasion-virulence-and-niche-adaptation-in-non-typeable-haemophilus-influenzae
#19
John M Atack, Yogitha N Srikhanta, Kate L Fox, Joseph A Jurcisek, Kenneth L Brockman, Tyson A Clark, Matthew Boitano, Peter M Power, Freda E-C Jen, Alastair G McEwan, Sean M Grimmond, Arnold L Smith, Stephen J Barenkamp, Jonas Korlach, Lauren O Bakaletz, Michael P Jennings
Non-typeable Haemophilus influenzae contains an N(6)-adenine DNA-methyltransferase (ModA) that is subject to phase-variable expression (random ON/OFF switching). Five modA alleles, modA2, modA4, modA5, modA9 and modA10, account for over two-thirds of clinical otitis media isolates surveyed. Here, we use single molecule, real-time (SMRT) methylome analysis to identify the DNA-recognition motifs for all five of these modA alleles. Phase variation of these alleles regulates multiple proteins including vaccine candidates, and key virulence phenotypes such as antibiotic resistance (modA2, modA5, modA10), biofilm formation (modA2) and immunoevasion (modA4)...
2015: Nature Communications
https://www.readbyqxmd.com/read/26140244/restoration-of-natural-killer-activity-in-hepatocellular-carcinoma-by-treatment-with-antibody-against-granulin-epithelin-precursor
#20
Phyllis Fy Cheung, Chi Wai Yip, Linda Wc Ng, Chun Kwok Wong, Tan To Cheung, Chung Mau Lo, Sheung Tat Fan, Siu Tim Cheung
Impairment of natural killer (NK) cell activity is an important mechanism of tumor immunoevasion. We have previously shown that expression of granulin-epithelin precursor (GEP) in hepatocellular carcinoma (HCC) cells rendered the cells resistant to NK cell immunosurveillance. Here, we examined whether targeting GEP could rescue NK activity in HCC patients. The current study demonstrated that quantities and activities of NK cells were significantly lower in HCC patients compared with healthy individuals, and were negatively correlated with GEP levels in HCC cells...
July 2015: Oncoimmunology
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