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https://www.readbyqxmd.com/read/28231588/checkpoint-inhibition-in-head-and-neck-cancer-immune-therapeutic-options-limitations-and-beyond
#1
Bastian Höchst, Percy A Knolle
The immune system functions to defend the organism against infectious microorganisms but also against transformed cells. This key role of the immune system, in particular cancer-specific T cells, in eliminating cancer cells is compromised by various immune escape strategies employed by cancer cells and the cancer microenvironment. Here, we review the current knowledge about the immune escape mechanisms of cancer and the attempts to reconstitute cancer-specific immunity by using checkpoint inhibitors in head and neck squamous cell carcinoma...
February 24, 2017: ORL; Journal for Oto-rhino-laryngology and its related Specialties
https://www.readbyqxmd.com/read/28228569/no-evidence-of-beneficial-effects-of-plasmapheresis-in-natalizumab-associated-pml
#2
Doriana Landi, Nicola De Rossi, Sara Zagaglia, Cristina Scarpazza, Luca Prosperini, Maria Albanese, Fabio Buttari, Francesco Mori, Girolama Alessandra Marfia, Maria Pia Sormani, Ruggero Capra, Diego Centonze
OBJECTIVE: To examine retrospectively the effects of plasmapheresis (PLEX) on the survival and clinical outcomes of patients with multiple sclerosis (MS) and natalizumab (NTZ)-associated progressive multifocal leukoencephalopathy (PML). METHODS: The medical literature was searched for the terms natalizumab and progressive multifocal leukoencephalopathy. A total of 193 international and 34 Italian NTZ-PML cases were included. Clinical outcome was determined by comparing the patients' clinical status at PML diagnosis with status after PML resolution...
February 22, 2017: Neurology
https://www.readbyqxmd.com/read/28220418/in-vitro-ubiquitination-activity-assays-in-plant-immune-responses
#3
Giulia Furlan, Marco Trujillo
Ubiquitination is a central posttranslational modification that impinges on the fate of proteins. While attachment of K48-linked chains onto soluble proteins marks them for proteolysis via the 26S proteasome, mono-ubiquitination or K63-linked chains result in the endocytosis and sorting through the endomembrane system of integral membrane proteins, such as pattern recognition receptors. In vitro ubiquitination assays allow the biochemical analysis of all individual components of the ubiquitination machinery and its potential substrates...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28218745/human-%C3%AE-%C3%AE-t-cells-are-quickly-reconstituted-after-stem-cell-transplantation-and-show-adaptive-clonal-expansion-in-response-to-viral-infection
#4
Sarina Ravens, Christian Schultze-Florey, Solaiman Raha, Inga Sandrock, Melanie Drenker, Linda Oberdörfer, Annika Reinhardt, Inga Ravens, Maleen Beck, Robert Geffers, Constantin von Kaisenberg, Michael Heuser, Felicitas Thol, Arnold Ganser, Reinhold Förster, Christian Koenecke, Immo Prinz
To investigate how the human γδ T cell pool is shaped during ontogeny and how it is regenerated after transplantation of hematopoietic stem cells (HSCs), we applied an RNA-based next-generation sequencing approach to monitor the dynamics of the repertoires of γδ T cell antigen receptors (TCRs) before and after transplantation in a prospective cohort study. We found that repertoires of rearranged genes encoding γδ TCRs (TRG and TRD) in the peripheral blood of healthy adults were stable over time. Although a large fraction of human TRG repertoires consisted of public sequences, the TRD repertoires were private...
February 20, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28210571/unmasking-histoplasmosis-immune-reconstitution-inflammatory-syndrome-in-a-patient-recently-started-on-antiretroviral-therapy
#5
Reuben Kiggundu, Henry W Nabeta, Richard Okia, Joshua Rhein, Robert Lukande
Histoplasmosis is the most common endemic mycoses among HIV-infected people. Patients with suppressed cell immunity mainly due to HIV are at increased risk of disseminated disease. Dermatological manifestations of immune reconstitution inflammatory syndrome (IRIS) and cutaneous manifestations of histoplasmosis similar to an IRIS event have been previously described. We report the case of a 43-year-old male who presented with cutaneous disseminated histoplasmosis due to Histoplasma capsulatum var. capsulatum 4 months after the onset of the antiretroviral therapy and some improvement in the immune reconstitution...
October 2016: Autopsy & case reports
https://www.readbyqxmd.com/read/28209904/noninvasive-imaging-of-human-immune-responses-in-a-human-xenograft-model-of-graft-versus-host-disease
#6
Catharina H M J Van Elssen, Mohammad Rashidian, Vladimir Vrbanac, Kai W Wucherpfennig, Zeina El Habre, Jana Sticht, Christian Freund, Johanne Jacobsen, Juanjo Cragnolini, Jessica Ingram, Loes Plaisier, Eric Spierings, Andrew M Tager, Hidde Ploegh
The immune system plays a crucial role in many diseases. Activation or suppression of immunity is often related to clinical outcome. Methods to explore the dynamics of immune responses are important to elucidate their role in conditions characterized by inflammation, such as infectious disease, cancer or auto-immunity. Immuno-PET is a non-invasive method by which disease and immune cell infiltration can be explored simultaneously. Using radiolabeled antibodies or fragments derived from them, it is possible to image disease-specific antigens and immune cell subsets...
February 16, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28209721/the-cumulative-burden-of-double-stranded-dna-virus-detection-after-allogeneic-hct-is-associated-with-increased-mortality
#7
Joshua A Hill, Bryan T Mayer, Hu Xie, Wendy M Leisenring, Meei-Li Huang, Terry Stevens-Ayers, Filippo Milano, Colleen Delaney, Mohamed L Sorror, Brenda M Sandmaier, Garrett Nichols, Danielle M Zerr, Keith R Jerome, Joshua T Schiffer, Michael Boeckh
Strategies to prevent active infection with certain double-stranded DNA (dsDNA) viruses after allogeneic hematopoietic cell transplantation (HCT) are limited by incomplete understanding of their epidemiology and clinical impact. We retrospectively tested weekly plasma samples from allogeneic HCT recipients at our center from 2007-2014. We used quantitative PCR to test for cytomegalovirus (CMV), BK polyomavirus (BKV), human herpesvirus 6B (HHV-6B), HHV-6A, adenovirus (AdV), and Epstein-Barr virus (EBV) between days 0-100 post-HCT...
February 16, 2017: Blood
https://www.readbyqxmd.com/read/28209523/tb-iris-proteomic-analysis-of-in-vitro-pbmc-responses-to-mycobacterium-tuberculosis-and-response-modulation-by-dexamethasone
#8
Liam Bell, Janique M Peyper, Shaun Garnett, Rabecca Tadokera, Robert Wilkinson, Graeme Meintjes, Jonathan M Blackburn
Paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) occurs in 8-54% of South African patients undergoing treatment for tuberculosis/human immunodeficiency virus co-infection. Improved TB-IRIS molecular pathogenesis understanding would enhance risk stratification, diagnosis, prognostication, and treatment. We assessed how TB-IRIS status and dexamethasone influence leukocyte proteomic responses to Mycobacterium tuberculosis (Mtb). Patient blood was obtained three weeks post-anti-retroviral therapy initiation...
February 14, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/28198424/human-ido-competent-long-lived-immunoregulatory-dendritic-cells-induced-by-intracellular-pathogen-and-their-fate-in-humanized-mice
#9
Rajeev K Tyagi, Brodie Miles, Rajesh Parmar, Neeraj K Garg, Sarat K Dalai, Babak Baban, Christopher W Cutler
Targeting of myeloid-dendritic cell receptor DC-SIGN by numerous chronic infectious agents, including Porphyromonas gingivalis, is shown to drive-differentiation of monocytes into dysfunctional mDCs. These mDCs exhibit alterations of their fine-tuned homeostatic function and contribute to dysregulated immune-responses. Here, we utilize P. gingivalis mutant strains to show that pathogen-differentiated mDCs from primary human-monocytes display anti-apoptotic profile, exhibited by elevated phosphorylated-Foxo1, phosphorylated-Akt1, and decreased Bim-expression...
February 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28195232/hematopoietic-pannexin-1-function-is-critical-for-neuropathic-pain
#10
Janelle L Weaver, Sanja Arandjelovic, Gregory Brown, Suresh K Mendu, Michael S Schappe, Monica W Buckley, Yu-Hsin Chiu, Shaofang Shu, Jin K Kim, Joyce Chung, Julia Krupa, Vesna Jevtovic-Todorovic, Bimal N Desai, Kodi S Ravichandran, Douglas A Bayliss
Neuropathic pain symptoms respond poorly to available therapeutics, with most treated patients reporting unrelieved pain and significant impairment in daily life. Here, we show that Pannexin 1 (Panx1) in hematopoietic cells is required for pain-like responses following nerve injury in mice, and a potential therapeutic target. Panx1 knockout mice (Panx1(-/-)) were protected from hypersensitivity in two sciatic nerve injury models. Bone marrow transplantation studies show that expression of functional Panx1 in hematopoietic cells is necessary for mechanical hypersensitivity following nerve injury...
February 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28194324/cell-therapies-in-cardiomyopathy-current-status-of-clinical-trials
#11
REVIEW
Ming Hao, Richard Wang, Wen Wang
Because the human heart has limited potential for regeneration, the loss of cardiomyocytes during cardiac myopathy and ischaemic injury can result in heart failure and death. Stem cell therapy has emerged as a promising strategy for the treatment of dead myocardium, directly or indirectly, and seems to offer functional benefits to patients. The ideal candidate donor cell for myocardial reconstitution is a stem-like cell that can be easily obtained, has a robust proliferation capacity and a low risk of tumour formation and immune rejection, differentiates into functionally normal cardiomyocytes, and is suitable for minimally invasive clinical transplantation...
2017: Analytical Cellular Pathology (Amsterdam)
https://www.readbyqxmd.com/read/28192188/hepatitis-c-virus-induced-nk-cell-activation-causes-metzincin-mediated-cd16-cleavage-and-impaired-antibody-dependent-cytotoxicity
#12
Barbara Oliviero, Stefania Mantovani, Stefania Varchetta, Dalila Mele, Giulia Grossi, Serena Ludovisi, Elisa Nuti, Armando Rossello, Mario U Mondelli
BACKGROUND & AIMS: The Fc receptor family for IgG type III (FcγRIII, CD16) is an activating receptor on natural killer (NK) cells and an essential mediator of antibody-dependent cellular cytotoxicity (ADCC). There is only limited information on its role during chronic hepatitis C virus (HCV) infection. We studied CD16 expression in relation to NK cell functional activity in HCV-infected patients and sought mechanistic insights into virus-induced modulation. METHODS: NK cell CD16 expression and activation status were evaluated ex vivo by flow cytometry in HCV-infected patients and healthy controls (HC) as well as in vitro after co-culture with HCV-infected Huh 7...
February 9, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28191773/notch-expanded-murine-hematopoietic-stem-and-progenitor-cells-mitigate-death-from-lethal-radiation-and-convey-immune-tolerance-in-mismatched-recipients
#13
Filippo Milano, Fabiola Merriam, Ian Nicoud, Jianqiang Li, Ted A Gooley, Shelly Heimfeld, Suzan Imren, Colleen Delaney
The hematopoietic syndrome of acute radiation syndrome (h-ARS) is characterized by severe bone marrow aplasia, resulting in a significant risk for bleeding, infections, and death. To date, clinical management of h-ARS is limited to supportive care dictated by the level of radiation exposure, with a high incidence of mortality in those exposed to high radiation doses. The ideal therapeutic agent would be an immediately available, easily distributable single-agent therapy capable of rapid in vivo hematopoietic reconstitution until recovery of autologous hematopoiesis occurs...
February 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28191009/defective-il-23-il-17-axis-protects-p47phox-mice-from-colon-cancer
#14
Cornelia Richter, Martina Herrero San Juan, Benno Weigmann, Dominik Bergis, Katrin Dauber, Michael H Muders, Gustavo B Baretton, Josef Martin Pfeilschifter, Halvard Bonig, Sebastian Brenner, Heinfried H Radeke
In the colon, a sophisticated balance between immune reaction and tolerance is absolutely required. Dysfunction may lead to pathologic phenotypes ranging from chronic inflammatory processes to cancer development. Two prominent modulators of colon inflammation are represented by the closely related cytokines interleukin (IL)-12 and IL-23, which initiate adaptive Th1 and Th17 immune responses, respectively. In this study, we investigated the impact of the NADPH oxidase protein p47phox, which negatively regulates IL-12 in dendritic cells, on colon cancer development in a colitis-associated colon cancer model...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28188718/-hematopoietic-stem-cells-transplant-in-patients-with-common-variable-immunodeficiency-is-a-therapeutic-option
#15
Julio César Cambray-Gutiérrez, Diana Andrea Herrera-Sánchez, Patricia López-Pérez, Aurora Chávez-García, Marco Antonio Yamazaki-Nakashimada
BACKGROUND: Patients with common variable immunodeficiency show higher incidence of sinopulmonary and gastrointestinal infections, as well as lymphoproliferative and autoimmune diseases. The treatment of choice is replacement therapy with human gamma-globulin. Hematopoietic stem cell transplantation is a non-conventional therapeutic modality. CASE REPORT: Twenty-six-year old woman with no family or hereditary history of primary immune deficiencies or consanguinity, with repeated episodes of otitis, sinusitis, gastroenteritis and bronchitis since childhood...
January 2017: Revista Alergia Mexico: Organo Oficial de la Sociedad Mexicana de Alergia e Inmunología, A.C
https://www.readbyqxmd.com/read/28182675/comparing-longitudinal-cd4-responses-to-cart-among-non-perinatally-hiv-infected-youth-versus-adults-results-from-the-hivrn-cohort
#16
Allison L Agwu, John A Fleishman, Guy Mahiane, Bareng Aletta Sanny Nonyane, Keri N Althoff, Baligh R Yehia, Stephen A Berry, Richard Rutstein, Ank Nijhawan, Christopher Mathews, Judith A Aberg, Jeanne C Keruly, Richard D Moore, Kelly A Gebo
BACKGROUND: Youth have residual thymic tissue and potentially greater capacity for immune reconstitution than adults after initiation of combination antiretroviral therapy (cART). However, youth face behavioral and psychosocial challenges that may make them more likely than adults to delay ART initiation and less likely to attain similar CD4 outcomes after initiating cART. This study compared CD4 outcomes over time following cART initiation between ART-naïve non-perinatally HIV-infected (nPHIV) youth (13-24 years-old) and adults (≥25-44 years-old)...
2017: PloS One
https://www.readbyqxmd.com/read/28176791/il-36%C3%AE-is-a-crucial-proximal-component-of-protective-type-1-mediated-lung-mucosal-immunity-in-gram-positive-and-negative-bacterial-pneumonia
#17
M A Kovach, B Singer, G Martinez-Colon, M W Newstead, X Zeng, P Mancuso, T A Moore, S L Kunkel, M Peters-Golden, B B Moore, T J Standiford
Interleukin-36γ (IL-36γ) is a member of novel IL-1-like proinflammatory cytokine family that are highly expressed in epithelial tissues and several myeloid-derived cell types. Little is known about the role of the IL-36 family in mucosal immunity, including lung anti-bacterial responses. We used murine models of IL-36γ deficiency to assess the contribution of IL-36γ in the lung during experimental pneumonia. Induction of IL-36γ was observed in the lung in response to Streptococcus pneumoniae (Sp) infection, and mature IL-36γ protein was secreted primarily in microparticles...
February 8, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28176790/architectural-and-functional-alterations-of-the-small-intestinal-mucosa-in-classical-whipple-s-disease
#18
H-J Epple, J Friebel, V Moos, H Troeger, S M Krug, K Allers, K Schinnerling, A Fromm, B Siegmund, M Fromm, J D Schulzke, T Schneider
Classical Whipple's disease (CWD) affects the gastrointestinal tract and rather elicits regulatory than inflammatory immune reactions. Mechanisms of malabsorption, diarrhea, and systemic immune activation are unknown. We here analyzed mucosal architecture, barrier function, and immune activation as potential diarrheal trigger in specimens from 52 CWD patients. Our data demonstrate villus atrophy and crypt hyperplasia associated with epithelial apoptosis and reduced alkaline phosphatase expression in the duodenum of CWD patients...
February 8, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28170421/comprehensive-mapping-of-antigen-specific-t-cell-responses-in-hepatitis-c-virus-infected-patients-with-or-without-spontaneous-viral-clearance
#19
Chao Zhang, Rui Hua, Yuanyuan Cui, Shasha Wang, Hongqing Yan, Dongmei Li, Yonghong Zhang, Zhengkun Tu, Pei Hao, Xinyue Chen, Jin Zhong, Junqi Niu, Xia Jin
Elucidating protective immunity against HCV is important for the development of a preventative vaccine. We hypothesize that spontaneous resolution of acute HCV infection offers clue to protective immune responses, and that DAA therapy affects the quality and quantity of HCV-specific T cell responses. To test these hypotheses, we performed T cell epitope mapping in 111 HCV-infected individuals including 61 chronically HCV-1b (CHC-1b) infected, 24 chronically HCV-2a (CHC-2a) infected and 26 spontaneously recovered (SPR) patients with 376 overlapping peptides covering the entire HCV polyprotein...
2017: PloS One
https://www.readbyqxmd.com/read/28163944/immune-reconstitution-inflammatory-syndrome-opening-pandora-s-box
#20
Mariana Meireles, Conceição Souto Moura, Margarida França
One of the purposes of antiretroviral therapy (ART) is to restore the immune system. However, it can sometimes lead to an aberrant inflammatory response and paradoxical clinical worsening known as the immune reconstitution inflammatory syndrome (IRIS). We describe a 23-year-old male, HIV1 infected with a rapid progression phenotype, who started ART with TCD4+ of 53 cells/mm(3) (3,3%) and HIV RNA = 890000 copies/mL (6 log). Four weeks later he was admitted to the intensive care unit with severe sepsis...
2017: Case Reports in Infectious Diseases
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