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Immune evasion

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https://www.readbyqxmd.com/read/29159802/adenovirus-vector-based-prime-boost-vaccination-via-heterologous-routes-induces-cervicovaginal-cd8-t-cell-responses-against-hpv16-oncoproteins
#1
Nicolas Çuburu, Selina Khan, Cynthia D Thompson, Rina Kim, Jort Vellinga, Roland Zahn, Douglas R Lowy, Gert Scheper, John T Schiller
Recent advances in immunotherapy against cancer underscore the importance of T lymphocytes and tumor microenvironment, but few vaccines targeting cancer have been approved likely due in part to the dearth of common tumor antigens, insufficient immunogenicity and the evolution of immune evasion mechanisms during the progression to malignancy. Human papillomaviruses (HPV) are the primary etiologic agents of cervical cancer and progression from persistent HPV-infection to cervical intraepithelial lesions and eventually cancer requires persistent expression of the oncoproteins E6 and E7...
November 21, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29158430/characterization-of-stress-and-innate-immunity-resistance-of-wild-type-and-%C3%AE-p66-borrelia-burgdorferi
#2
Michael W Curtis, Beth L Hahn, Kai Zhang, Chunhao Li, Richard T Robinson, Jenifer Coburn
Borrelia burgdorferi is a causative agent of Lyme disease, the most common arthropod-borne disease in the United States. B. burgdorferi evades host immune defenses to establish a persistent, disseminated infection. Previous work showed that P66-deficient B. burgdorferi (Δp66) is cleared quickly after inoculation in mice. We demonstrate that Δp66 is rapidly cleared from the skin inoculation site prior to dissemination. The rapid clearance of Δp66 is not due to inherent defects in multiple properties that might affect infectivity: bacterial outer membrane integrity, motility, chemotactic response, or nutrient acquisition...
November 20, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/29158081/streptococcus-pyogenes-nuclease-a-spna-mediated-virulence-does-not-exclusively-depend-on-nuclease-activity
#3
Callum Chalmers, Adrina Hema J Khemlani, Chae Ryeong Sohn, Jacelyn Mei San Loh, Catherine Jia-Yun Tsai, Thomas Proft
BACKGROUND: Streptococcus pyogenes, or Group A Streptococcus (GAS), is a human pathogen that causes a wide range of diseases, including pharyngitis, necrotizing fasciitis and toxic shock syndrome. The bacterium produces a large arsenal of virulence factors, including the cell wall-anchored Streptococcus pyogenes nuclease A (SpnA), which facilitates immune evasion by degrading the DNA backbone of neutrophil extracellular traps. SpnA consists of a C-terminal endo/exonuclease domain and a N-terminal domain of unknown function...
November 13, 2017: Journal of Microbiology, Immunology, and Infection, Wei Mian Yu Gan Ran za Zhi
https://www.readbyqxmd.com/read/29157967/the-role-of-interferon-in-persistent-viral-infection-insights-from-murine-norovirus
#4
REVIEW
Timothy J Nice, Bridget A Robinson, Jacob A Van Winkle
Persistent viral infections result from evasion or avoidance of sterilizing immunity, extend the timeframe of virus transmission, and can trigger disease. Prior studies in mouse models of persistent infection have suggested that ineffective adaptive immune responses are necessary for persistent viral infection. However, recent work in the murine norovirus (MNV) model of persistent infection demonstrates that innate immunity can control both early and persistent viral replication independently of adaptive immune effector functions...
November 17, 2017: Trends in Microbiology
https://www.readbyqxmd.com/read/29154043/the-cause-and-effect-of-cryptococcus-interactions-with-the-host
#5
REVIEW
Elizabeth R Ballou, Simon A Johnston
Upon Cryptococcus neoformans infection of the host lung, the fungus enters a nutrient poor environment and must adapt to a variety of host-specific stress conditions (temperature, nutrient limitation, pH, CO2). Fungal spores enter this milieu with limited nutritional reserves, germinate, and begin proliferating by budding as yeast. Although relatively little is known about the initial stages of infection, recent work has characterized changes that occur upon germination. This program and subsequent yeast-phase proliferation progress in a dynamic environment as host nutrient immunity responds to the infection via toxic accumulation or sequestration of essential micronutrients and innate immune cells are recruited to the site of infection...
November 15, 2017: Current Opinion in Microbiology
https://www.readbyqxmd.com/read/29152681/trichothecenes-immunomodulatory-effects-mechanisms-and-anti-cancer-potential
#6
REVIEW
Qinghua Wu, Xu Wang, Eugenie Nepovimova, Anca Miron, Qianying Liu, Yun Wang, Dongxiao Su, Hualin Yang, Li Li, Kamil Kuca
Paradoxically, trichothecenes have both immunosuppressive and immunostimulatory effects. The underlying mechanisms have not been fully explored. Early studies show that dose, exposure timing, and the time at which immune function is assessed influence whether trichothecenes act in an immunosuppressive or immunostimulatory fashion. Recent studies suggest that the immunomodulatory function of trichothecenes is also actively shaped by competing cell-survival and death-signaling pathways. Autophagy may also promote trichothecene immunosuppression, although the mechanism may be complicated...
November 20, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/29152083/programmed-cell-death-1-expression-is-associated-with-inferior-survival-in-patients-with-primary-central-nervous-system-lymphoma
#7
Hyunsoo Cho, Se Hoon Kim, Soo-Jeong Kim, Jong Hee Chang, Woo-Ick Yang, Chang-Ok Suh, Yu Ri Kim, Ji Eun Jang, June-Won Cheong, Yoo Hong Min, Jin Seok Kim
Programmed cell death 1 (PD-1) and its ligands PD-L1/PD-L2 have been shown to mediate immune evasion in various cancers, but their prognostic implications in patients with primary central nervous system lymphoma (PCNSL) are poorly understood. Therefore, we analyzed 76 PCNSL patients at initial diagnosis who were treated homogenously with high-dose methotrexate-based chemotherapy, and evaluated the prognostic roles of high immunohistochemical PD-1, PD-L1, and PD-L2 expression. The cut-off values for high PD-1 (≥ 70 cells/high power field [HPF]), PD-L1 (≥ 100 cells/HPF), and PD-L2 (≥ 100 cells/HPF) were determined by the area under the receiver operating characteristic curve...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29147622/factors-released-by-the-tumor-far-microenvironment-are-decisive-for-pancreatic-adenocarcinoma-development-and-progression
#8
REVIEW
Juan L Iovanna, Daniel Closa
The REG3β protein was identified more than 2 decades ago, but its role in PDAC development was only recently reported. In Pancreatic Ductal Adenocarcinoma (PDAC), REG3β protein is expressed and released by the far microenvironment, which is situated out of the tumor, at the periphery of the tumor mass, and is part of the healthy peri-tumoral region. This compartment is completely unrelated to the classical microenvironment that corresponds to the intra-tumoral stoma. Clinically relevant, the far microenvironment, and the factors released by it, could be novel and original therapeutic targets for treating patients with a PDAC...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29147618/programmed-cell-death-ligands-expression-in-phaeochromocytomas-and-paragangliomas-relationship-with-the-hypoxic-response-immune-evasion-and-malignant-behavior
#9
David J Pinato, James R Black, Sebastian Trousil, Roberto E Dina, Pritesh Trivedi, Francesco A Mauri, Rohini Sharma
The hypoxic response underlies the pathogenesis and malignant behavior of PCC/PGL. Regulation of PD-1 receptor-ligand signaling, a therapeutically actionable driver of the anti-tumor immune response, is a hypoxic-driven trait across malignancies. We evaluated the prognostic role of PD ligands in association with biomarkers of hypoxia and angiogenesis in patients with PCC/PGL. Tissue microarrays sections including consecutive cases diagnosed between 1983-2011 were stained for PD-L1 and 2, hypoxia inducible factor 1a (Hif-1a), Carbonic Anhydrase IX (CaIX), Vascular Endothelial Growth Factor-A (VEGF-A)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29147604/tap1-down-regulation-elicits-immune-escape-and-poor-prognosis-in-colorectal-cancer
#10
Agnes Ling, Anna Löfgren-Burström, Pär Larsson, Xingru Li, Maria L Wikberg, Åke Öberg, Roger Stenling, Sofia Edin, Richard Palmqvist
The anti-tumor immune response has been shown to be of great prognostic importance in colorectal cancer (CRC) and so has the tumors ability for immune evasion. Our aim of this study was to investigate tumor factors that influence immunity. We used a gene expression array to search for potential mechanisms of tumor immune escape. One candidate gene identified was TAP1, involved in antigen presentation by MHC class I. TAP1 protein expression was evaluated by immunohistochemistry in 436 CRC patients of the Colorectal Cancer in Umeå Study cohort...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29146805/the-structural-basis-of-flagellin-detection-by-naip5-a-strategy-to-limit-pathogen-immune-evasion
#11
Jeannette L Tenthorey, Nicole Haloupek, José Ramón López-Blanco, Patricia Grob, Elise Adamson, Ella Hartenian, Nicholas A Lind, Natasha M Bourgeois, Pablo Chacón, Eva Nogales, Russell E Vance
Robust innate immune detection of rapidly evolving pathogens is critical for host defense. Nucleotide-binding domain leucine-rich repeat (NLR) proteins function as cytosolic innate immune sensors in plants and animals. However, the structural basis for ligand-induced NLR activation has so far remained unknown. NAIP5 (NLR family, apoptosis inhibitory protein 5) binds the bacterial protein flagellin and assembles with NLRC4 to form a multiprotein complex called an inflammasome. Here we report the cryo-electron microscopy structure of the assembled ~1...
November 17, 2017: Science
https://www.readbyqxmd.com/read/29145543/association-of-ipilimumab-with-safety-and-antitumor-activity-in-women-with-metastatic-or-recurrent-human-papillomavirus-related-cervical-carcinoma
#12
Stephanie Lheureux, Marcus O Butler, Blaise Clarke, Mihaela C Cristea, Lainie P Martin, Katia Tonkin, Gini F Fleming, Anna V Tinker, Hal W Hirte, Daliah Tsoref, Helen Mackay, Neesha C Dhani, Prafull Ghatage, Johanne Weberpals, Stephen Welch, Nhu-An Pham, Vinicius Motta, Valentin Sotov, Lisa Wang, Katherine Karakasis, Smitha Udagani, Suzanne Kamel-Reid, Howard Z Streicher, Patricia Shaw, Amit M Oza
Importance: Based on evidence of human papillomavirus (HPV)-induced immune evasion, immunotherapy may be an attractive strategy in cervical cancer. Ipilimumab is a fully humanized monoclonal antibody that blocks cytotoxic T-lymphocyte antigen-4 (CTLA-4), which acts to downregulate the T-cell immune response. Objective: To assess the safety and antitumor activity of ipilimumab in recurrent cervical cancer. Design, Setting, and Participants: A multicenter trial was designed for patients with metastatic cervical cancer (squamous cell carcinoma or adenocarcinoma) with measurable disease and progression after at least 1 line of platinum chemotherapy...
November 16, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/29144218/characterization-of-a-glycine-rich-protein-from-rhipicephalus-microplus-tissue-expression-gene-silencing-and-immune-recognition
#13
B F Leal, M F Alzugaray, A Seixas, I Da Silva Vaz, C A S Ferreira
Salivary molecules, as glycine-rich proteins (GRPs), are essential to tick attachment and feeding on the host and are suggested to be involved in the host's immune system evasion, therefore representing natural candidates in the search for protective vaccine antigens. This work shows the molecular characterization of a GRP from Rhipicephalus microplus (RmGRP). The cDNA and putative amino acid sequences were analysed, as well as the transcription level in tick tissues/developmental stages, showing the highest levels of gene expression in 1-day-old larvae and salivary glands of fully engorged females...
November 16, 2017: Parasitology
https://www.readbyqxmd.com/read/29143962/comparison-of-gene-expression-in-post-smolt-atlantic-salmon-challenged-by-lf-89-like-and-em-90-like-piscirickettsia-salmonis-isolates-reveals-differences-in-the-immune-response-associated-with-pathogenicity
#14
M Rozas-Serri, A Peña, G Arriagada, R Enríquez, L Maldonado
Piscirickettsiosis is the main bacterial disease affecting the Chilean salmon farming industry and is responsible for high economic losses. The aim of this study was to describe and comparatively quantify the immune response of post-smolt Atlantic salmon infected by cohabitation with fish bearing LF-89-like and EM-90-like Piscirickettsia salmonis. The expression of 17 genes related to the immune response was studied in head kidney from cohabitant fish by RT-qPCR. Our results at the transcriptomic level suggest that P...
November 16, 2017: Journal of Fish Diseases
https://www.readbyqxmd.com/read/29142125/emergence-of-double-and-triple-gene-reassortant-g1p-8-rotaviruses-possessing-a-ds-1-like-backbone-post-rotavirus-vaccine-introduction-in-malawi
#15
Khuzwayo C Jere, Chrispin Chaguza, Naor Bar-Zeev, Jenna Lowe, Chikondi Peno, Benjamin Kumwenda, Osamu Nakagomi, Jacqueline E Tate, Umesh D Parashar, Robert S Heyderman, Neil French, Nigel A Cunliffe, Iturriza-Gomara Miren
To combat the high burden of rotavirus gastroenteritis, multiple African countries have introduced rotavirus vaccines into their childhood immunisation programmes. Malawi incorporated a G1P[8] rotavirus vaccine (Rotarix™) into its immunisation schedule in 2012. Utilising a surveillance platform of hospitalised rotavirus gastroenteritis cases, we examined the phylodynamics of G1P[8] rotavirus strains that circulated in Malawi before (1998 - 2012) and after (2013 - 2014) vaccine introduction. Analysis of whole genomes obtained through next generation sequencing revealed that all randomly-selected pre-vaccine G1P[8] strains sequenced (n=32) possessed a Wa-like genetic constellation, whereas post-vaccine G1P[8] strains (n=18) had a DS-1-like constellation...
November 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29139623/extracellular-proteinases-of-candida-species-pathogenic-yeasts
#16
Maria Rapala-Kozik, Oliwia Bochenska, Dorota Zajac, Justyna Karkowska-Kuleta, Mariusz Gogol, Marcin Zawrotniak, Andrzej Kozik
The increased incidence of severe disseminated infections caused by opportunistic yeast-like fungi Candida spp. highlights the urgent need for research into the major virulence factors of these pathogens - extracellular aspartic proteinases of the candidapepsin and yapsin families. Classically, these enzymes were considered to be generally destructive factors that damage host tissues and provide nutrients for pathogen propagation. However, in recent decades, novel and more specific functions have been suggested for extracellular candidal proteinases...
November 15, 2017: Molecular Oral Microbiology
https://www.readbyqxmd.com/read/29138368/-regulatory-mechanisms-of-pd-l1-expression-and-its-role-in-immune-evasion
#17
Keisuke Kataoka
Immune checkpoint blockade therapy using anti-PD-1 or anti-PD-L1 antibodies can unleash anti-tumor immunity and induce durable remission in a variety ofhuman cancers. However, the regulatory mechanisms of PD-L1 expression mediating immune evasion ofcancer cells have not been fully elucidated, including the genetic alterations causing PD-L1 overexpression. Recently, we have reported a novel genetic mechanism ofimmune evasion associated with structural variations(SVs)disrupting the 3'-untranslated region(UTR)ofthe PD-L1 gene in various malignancies, such as aggressive lymphomas and gastrointestinal cancers...
November 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/29137278/comprehensive-microrna-sequencing-of-exosomes-derived-from-head-and-neck-carcinoma-cells-in-vitro-reveals-common-secretion-profiles-and-potential-utility-as-salivary-biomarkers
#18
Scott Langevin, Damaris Kuhnell, Tess Parry, Jacek Biesiada, Shouxiong Huang, Trisha Wise-Draper, Keith Casper, Xiang Zhang, Mario Medvedovic, Susan Kasper
Exosomes are nano-scale, membrane encapsulated vesicles that are released by cells into the extracellular space and function as intercellular signaling vectors through horizontal transfer of biologic molecules, including microRNA (miRNA). There is evidence that cancer-derived exosomes enable the tumor to manipulate its microenvironment, thus contributing to the capacity of the tumor for immune evasion, growth, invasion, and metastatic spread. The objective of this study was to characterize differential secretion of exosomal miRNA by head and neck squamous cell carcinoma (HNSCC) and identify a set of candidate biomarkers that could be detected in non-invasive saliva samples...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137273/programmed-death-ligand-1-and-met-co-expression-is-a-poor-prognostic-factor-in-gastric-cancers-after-resection
#19
Mi Jung Kwon, Kab-Choong Kim, Eun Sook Nam, Seong Jin Cho, Hye-Rim Park, Soo Kee Min, Jinwon Seo, Ji-Young Choe, Hye Kyung Lee, Ho Suk Kang, Kyueng-Whan Min
Programmed death-ligand 1 (PD-L1) plays an essential protein for immune evasion, contributing to tumor development and progression. Recent studies have reported MET as an upregulator for PD-L1 overexpression through an oncogenic pathway. However, an association between PD-L1 expression with MET has not been reported in gastric cancer.The prognostic significance of PD-L1 and its association with Epstein-Barr virus (EBV), microsatellite instability (MSI), and mucin phenotype remain controversial. We performed in situ hybridization for EBV-encoded RNA and immunohistochemistry in tissue microarrays for 394 gastric cancers...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29133133/boosting-natural-killer-cell-based-immunotherapy-with-anticancer-drugs-a-perspective
#20
REVIEW
Loredana Cifaldi, Franco Locatelli, Emiliano Marasco, Lorenzo Moretta, Vito Pistoia
Natural killer (NK) cells efficiently recognize and kill tumor cells through several mechanisms including the expression of ligands for NK cell-activating receptors on target cells. Different clinical trials indicate that NK cell-based immunotherapy represents a promising antitumor treatment. However, tumors develop immune-evasion strategies, including downregulation of ligands for NK cell-activating receptors, that can negatively affect antitumor activity of NK cells, which either reside endogenously, or are adoptively transferred...
November 10, 2017: Trends in Molecular Medicine
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