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https://www.readbyqxmd.com/read/28432648/rationale-for-new-checkpoint-inhibitor-combinations-in-melanoma-therapy
#1
Mario Mandalà, Carlo Tondini, Barbara Merelli, Daniela Massi
The use of monoclonal antibodies that block immunologic checkpoints, which mediate adaptive immune resistance, has revolutionized the treatment of metastatic melanoma patients. Specifically, targeting single immune suppressive molecules such as cytotoxic T lymphocyte-associated protein 4 (CTLA-4), or programmed cell death protein 1 (PD-1) expressed on T cells or its primary ligand, programmed cell death ligand 1 (PD-L1), resulted in pronounced clinical benefit for a subset of melanoma patients. Although single-agent immune checkpoint inhibitor therapy has demonstrated promising clinical activity in metastatic melanoma patients, there is still a significant proportion of patients who show primary resistance to these therapies...
April 21, 2017: American Journal of Clinical Dermatology
https://www.readbyqxmd.com/read/28432326/a-novel-mechanism-linking-memory-stem-cells-with-innate-immunity-in-protection-against-hiv-1-infection
#2
Yufei Wang, Trevor Whittall, Stuart Neil, Gary Britton, Mukesh Mistry, Supachai Rerks-Ngarm, Punnee Pitisuttithum, Jaranit Kaewkungwal, Sorachai Nitayaphan, Xuesong Yu, Alicia Sato, Robert J O'Connell, Nelson L Michael, Merlin L Robb, Jerome H Kim, Thomas Lehner
HIV infection affects 37 million people and about 1.7 million are infected annually. Among the phase III clinical trials only the RV144 vaccine trial elicited significant protection against HIV-1 acquisition, but the efficacy and immune memory were inadequate. To boost these vaccine functions we studied T stem cell memory (TSCM) and innate immunity. TSCM cells were identified by phenotypic markers of CD4(+) T cells and they were further characterised into 4 subsets. These expressed the common IL-2/IL-15 receptors and another subset of APOBEC3G anti-viral restriction factors, both of which were upregulated...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28432146/c1q-dependent-dendritic-cell-cross-presentation-of-in-vivo-formed-antigen-antibody-complexes
#3
Nataschja I Ho, Marcel G M Camps, Edwin F E de Haas, Leendert A Trouw, J Sjef Verbeek, Ferry Ossendorp
Dendritic cells (DCs) are specialized in Ag engulfment via a wide variety of uptake receptors on their cell surface. In the present study we investigated Ag uptake and presentation of in vivo-formed Ag-Ab complexes by i.v. injecting mice with Ag-specific Abs followed by the cognate Ag. We show by this natural Ab-mediated Ag targeting system that uptake by splenic APC subsets is severely hampered in mice lacking complement factor C1q (C1qa(-/-)). Moreover, no detectable Ag cross-presentation by CD8α(+) DCs from C1qa(-/-) mice was found...
April 21, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28431200/the-utility-of-flow-cytometry-in-differentiating-nk-t-cell-lymphoma-from-indolent-and-reactive-nk-cell-proliferations
#4
Sanjay de Mel, Jenny Bei Li, Muhammad Bilal Abid, Tiffany P L Tang, Hui Ming Tay, Wen Chang Ting, Li Mei Poon, Tae Hoon Chung, Benjamin Mow, Allison Tso, Kiat Hoe Ong, Wee Joo Chng, Te Chih Liu
BACKGROUND: The WHO defines 3 categories of NK cell malignancies; extra nodal NK/T cell lymphoma (NKTCL), aggressive NK cell leukaemia, and the provisional entity chronic lymphoproliferative disorder of NK cells (CLPD-NK). Although the flow cytometric (FC) phenotype of CLPD-NK has been described, studies on FC phenotype of NKTCL are limited. To the best of our knowledge ours is the first study to compare the phenotype of NKTCL, CLPD-NK, reactive NK lymphocytosis (RNKL), and normal NK cells using eight colour (8C) FC...
April 21, 2017: Cytometry. Part B, Clinical Cytometry
https://www.readbyqxmd.com/read/28431111/correction-of-abnormal-b-cell-subset-distribution-by-interleukin-6-receptor-blockade-in-polymyalgia-rheumatica
#5
Guillermo Carvajal Alegria, Valérie Devauchelle-Pensec, Yves Renaudineau, Alain Saraux, Jacques-Olivier Pers, Divi Cornec
Objectives.: The aim was to study lymphocyte subsets and circulating cytokines at diagnosis of PMR and after tocilizumab monotherapy. Methods.: Eighteen untreated patients with PMR were included in a prospective study and received 3-monthly tocilizumab infusions without glucocorticoids. Lymphocyte subset distribution was assessed by flow cytometry and serum cytokines were assayed by a 34-cytokine array and ELISA, at baseline and during follow-up. Baseline data were also compared with age- and sex-matched controls...
April 20, 2017: Rheumatology
https://www.readbyqxmd.com/read/28431019/identifying-cytomegalovirus-cmv-complications-using-the-quantiferon-cmv-assay-after-allogeneic-hematopoietic-stem-cell-transplantation
#6
Michelle K Yong, Paul U Cameron, Monica Slavin, C Orla Morrissey, Krystal Bergin, Andrew Spencer, David Ritchie, Allen C Cheng, Assia Samri, Guislaine Carcelain, Brigitte Autran, Sharon R Lewin
Background: Cytomegalovirus (CMV) reactivation and disease remain a major cause of morbidity and mortality in hematopoietic stem cell transplant (HSCT) recipients. A simple test to identify recovery of CMV-specific T-cell immunity could assist clinicians in managing CMV-related complications. Methods: In an observational multi-centre prospective study of 94 allogeneic HSCT recipients we evaluated CMV-specific T-cell immunity at baseline, 3, 6, 9 and 12 months post-transplant using the Quantiferon-CMV®, an ELISpot assay and in a subset, we also evaluated intracellular cytokine staining (ICS)...
April 18, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28431010/clinical-trial-of-the-anti-pd-l1-antibody-bms-936559-in-hiv-1-infected-participants-on-suppressive-antiretroviral-therapy
#7
Cynthia L Gay, Ronald J Bosch, Justin Ritz, Jason M Hataye, Evgenia Aga, Randall L Tressler, Stephen W Mason, Carey K Hwang, Dennis M Grasela, Neelanjana Ray, Josh C Cyktor, John M Coffin, Edward P Acosta, Richard A Koup, John W Mellors, Joseph J Eron
Background.: Reversing immune exhaustion with an anti-PD-L1 antibody may improve HIV-1-specific immunity and increase clearance of HIV-1 expressing cells. Methods.: Phase I, randomized, double-blind, placebo-controlled dose-escalating study of BMS-936559including HIV-1-infected adults ≥18 to ≤70 years on suppressive antiretroviral therapy with CD4+ counts ≥350 cells/μL and detectable plasma HIV-1 RNA by single copy assay. Data on single infusions of BMS-936559 (0...
April 18, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28430799/diagnostic-and-prognostic-value-of-long-noncoding-rnas-as-biomarkers-in-urothelial-carcinoma
#8
Johanna Droop, Tibor Szarvas, Wolfgang A Schulz, Christian Niedworok, Günter Niegisch, Kathrin Scheckenbach, Michèle J Hoffmann
Many long noncoding RNAs (lncRNAs) are deregulated in cancer and contribute to oncogenesis. In urothelial carcinoma (UC), several lncRNAs have been reported to be overexpressed and proposed as biomarkers. As most reports have not been confirmed independently in large tissue sets, we aimed to validate the diagnostic and prognostic value of lncRNA upregulation in independent cohorts of UC patients. Thus, expression of seven lncRNA candidates (GAS5, H19, linc-UBC1, MALAT1, ncRAN, TUG1, UCA1) was measured by RT-qPCR in cell lines and tissues and correlated to clinicopathological parameters including follow-up data (set 1: N n = 10; T n = 106)...
2017: PloS One
https://www.readbyqxmd.com/read/28430349/prognostic-significance-of-infiltrating-immune-cell-subtypes-in-invasive-ductal-carcinoma-of-the-breast
#9
Yangmei Xu, Suzhen Lan, Qiuhong Zheng
PURPOSE: To explore the correlation between tumor-infiltrating immune cell subsets and breast cancer prognosis. MATERIALS AND METHODS: Specimens of 102 patients with invasive ductal carcinoma of the breast were analyzed for immune-related markers (CD8, CD20, FOXP3 and CD68). The number of positive cells in the 3 most highly stained intratumoral stroma areas of the primary tumor was counted. The mean number was calculated and used to divide patients into 2 groups for each marker (CD8-high/CD8-low, CD20-high/CD20-low, FOXP3-high/FOXP3-low, and CD68-high/CD68-low)...
April 20, 2017: Tumori
https://www.readbyqxmd.com/read/28429232/detection-of-potential-metastatic-prostate-cancer-circulating-biomarkers-by-comparison-of-mirna-profiles-in-du145-cells-and-culture-medium
#10
K A Fomicheva, A I Osip'yants, E N Knyazev, T R Samatov, M Yu Shkurnikov
We studied the profile of miRNA secreted into culture medium by DU145 prostate cancer cells and identified a subset of miRNAs characterized by the absence of correlation of their content in the cell and medium, which is likely a result of specific secretion. Three of these miRNA, hsa-miR-4417, hsa-miR-3175, and hsa-miR-6782-5p, exhibit the highest expression and are candidate circulating biomarkers for metastatic activity of prostate cancer. Two of these miRNA are coded by introns of genes linked with genome stability maintenance and chromatin remodeling regulation...
April 21, 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28428882/differential-phenotypes-of-memory-cd4-and-cd8-t-cells-in-the-spleen-and-peripheral-tissues-following-immunostimulatory-therapy
#11
Gail D Sckisel, Annie Mirsoian, Christine M Minnar, Marka Crittenden, Brendan Curti, Jane Q Chen, Bruce R Blazar, Alexander D Borowsky, Arta M Monjazeb, William J Murphy
BACKGROUND: Studies assessing immune parameters typically utilize human PBMCs or murine splenocytes to generate data that is interpreted as representative of immune status. Using splenocytes, we have shown memory CD4-T cells that expand following systemic immunostimulatory therapies undergo rapid IFNg-mediated activation induced cell death (AICD) resulting in a net loss of total CD4-T cells which correlates with elevated PD-1 expression. This is in contrast to CD8-T cells which expand with minimal PD-1 upregulation and apoptosis...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28428879/a-systems-biology-approach-to-investigating-the-influence-of-exercise-and-fitness-on-the-composition-of-leukocytes-in-peripheral-blood
#12
Michael P Gustafson, Ara Celi DiCostanzo, Courtney M Wheatley, Chul-Ho Kim, Svetlana Bornschlegl, Dennis A Gastineau, Bruce D Johnson, Allan B Dietz
BACKGROUND: Exercise immunology has become a growing field in the past 20 years, with an emphasis on understanding how different forms of exercise affect immune function. Mechanistic studies are beginning to shed light on how exercise may impair the development of cancer or be used to augment cancer treatment. The beneficial effects of exercise on the immune system may be exploited to improve patient responses to cancer immunotherapy. METHODS: We investigated the effects of acute exercise on the composition of peripheral blood leukocytes over time in a male population of varying fitness...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28428369/single-cell-rna-seq-reveals-new-types-of-human-blood-dendritic-cells-monocytes-and-progenitors
#13
Alexandra-Chloé Villani, Rahul Satija, Gary Reynolds, Siranush Sarkizova, Karthik Shekhar, James Fletcher, Morgane Griesbeck, Andrew Butler, Shiwei Zheng, Suzan Lazo, Laura Jardine, David Dixon, Emily Stephenson, Emil Nilsson, Ida Grundberg, David McDonald, Andrew Filby, Weibo Li, Philip L De Jager, Orit Rozenblatt-Rosen, Andrew A Lane, Muzlifah Haniffa, Aviv Regev, Nir Hacohen
Dendritic cells (DCs) and monocytes play a central role in pathogen sensing, phagocytosis, and antigen presentation and consist of multiple specialized subtypes. However, their identities and interrelationships are not fully understood. Using unbiased single-cell RNA sequencing (RNA-seq) of ~2400 cells, we identified six human DCs and four monocyte subtypes in human blood. Our study reveals a new DC subset that shares properties with plasmacytoid DCs (pDCs) but potently activates T cells, thus redefining pDCs; a new subdivision within the CD1C(+) subset of DCs; the relationship between blastic plasmacytoid DC neoplasia cells and healthy DCs; and circulating progenitor of conventional DCs (cDCs)...
April 21, 2017: Science
https://www.readbyqxmd.com/read/28427421/cerebrospinal-fluid-csf-biomarkers-of-iron-status-are-associated-with-csf-viral-load-antiretroviral-therapy-and-demographic-factors-in-hiv-infected-adults
#14
Stephanie M Patton, Quan Wang, Todd Hulgan, James R Connor, Peilin Jia, Zhongming Zhao, Scott L Letendre, Ronald J Ellis, William S Bush, David C Samuels, Donald R Franklin, Harpreet Kaur, Jennifer Iudicello, Igor Grant, Asha R Kallianpur
BACKGROUND: HIV-associated neurocognitive disorder (HAND) remains common, despite antiretroviral therapy (ART). HIV dysregulates iron metabolism, but cerebrospinal fluid (CSF) levels of iron and iron-transport proteins in HIV-infected (HIV+) persons are largely unknown. The objectives of this study were to characterize CSF iron-related biomarkers in HIV+ adults and explore their relationships to known predictors of HAND. METHODS: We quantified total iron, transferrin and heavy-chain (H)-ferritin by immunoassay in CSF sampled by lumbar puncture in 403 HIV+ participants in a multi-center, observational study and evaluated biomarker associations with demographic and HIV-related correlates of HAND [e...
April 21, 2017: Fluids and Barriers of the CNS
https://www.readbyqxmd.com/read/28426803/dendritic-cell-maturation-but-not-type-i-interferon-exposure-restricts-infection-by-htlv-1-and-viral-transmission-to-t-cells
#15
Gergès Rizkallah, Sandrine Alais, Nicolas Futsch, Yuetsu Tanaka, Chloé Journo, Renaud Mahieux, Hélène Dutartre
Human T lymphotropic Virus type 1 (HTLV-1) is the etiological agent of Adult T cell Leukemia/Lymphoma (ATLL) and HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP). Both CD4+ T-cells and dendritic cells (DCs) infected with HTLV-1 are found in peripheral blood from HTLV-1 carriers. We previously demonstrated that monocyte-derived IL-4 DCs are more susceptible to HTLV-1 infection than autologous primary T-cells, suggesting that DC infection precedes T-cell infection. However, during blood transmission, breast-feeding or sexual transmission, HTLV-1 may encounter different DC subsets present in the blood, the intestinal or genital mucosa respectively...
April 20, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28426533/hiv-dna-content-in-different-cd4-t-cell-subsets-correlates-with-cd4-cd8-ratio-or-length-of-efficient-treatment
#16
Lara Gibellini, Simone Pecorini, Sara de Biasi, Elena Bianchini, Margherita Digaetano, Marcello Pinti, Gianluca Carnevale, Vanni Borghi, Giovanni Guaraldi, Cristina Mussini, Andrea Cossarizza, Milena Nasi
OBJECTIVES: HIV establishes a latent infection at different degrees within naïve (TN) or central (TCM) and effector memory (TEM) CD4+ T cell. Studying patients in whom HIV production was suppressed by combined antiretroviral therapy (cART), our main aim was to find which factors are related or can influence intracellular viral reservoir in different CD4+ T cell subsets. METHODS: We enrolled 32 HIV+ patients successfully treated for > 2 years, with a CD4+ T cell count > 500 cells/μL and plasma viremia undetectable from at least one year...
April 19, 2017: AIDS
https://www.readbyqxmd.com/read/28426456/expression-and-localization-of-mir-21-and-mir-126-in-mucosal-tissue-from-patients-with-inflammatory-bowel-disease
#17
Gorm Thorlacius-Ussing, Boye Schnack Nielsen, Vibeke Andersen, Kim Holmstrøm, Anders E Pedersen
BACKGROUND: microRNAs (miRNAs) are small noncoding RNAs that guide degradation of mRNA and regulate protein expression. miRNA based diagnostic biomarkers for ulcerative colitis (UC) and Crohn's disease (CD) are emerging but information about the cellular localization of many miRNAs is limited and more detailed histologic evaluation of miRNA expression patterns is needed to understand their immunobiological function. METHODS: Formalin-fixed paraffin-embedded colon biopsies from 10 patients with UC and 8 patients with CD together with 9 controls were examined by RT-qPCR and quantitative in situ hybridization (ISH)...
May 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28426455/digoxin-attenuates-murine-experimental-colitis-by-downregulating-th17-related-cytokines
#18
Shinya Tani, Ryosuke Takano, Satoshi Tamura, Shinji Oishi, Moriya Iwaizumi, Yasushi Hamaya, Kosuke Takagaki, Toshi Nagata, Shintaro Seto, Toshinobu Horii, Isao Kosugi, Toshihide Iwashita, Satoshi Osawa, Takahisa Furuta, Hiroaki Miyajima, Ken Sugimoto
BACKGROUND: Digoxin, a cardiac glycoside used for the treatment of heart failure, was reported to inhibit the retinoid-related orphan receptor gamma t (RORγt) and attenuate the severity of experimental autoimmune encephalomyelitis and arthritis in mice. However, the effects of digoxin in a mice model of inflammatory bowel disease have not been elucidated. METHODS: Colitis was induced in severe combined immunodeficiency mice by adoptive transfer of CD45RB CD4 T cells...
May 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28426172/distinct-roles-of-th17-and-th1-cells-in-inflammatory-responses-associated-with-the-presentation-of-paucibacillary-leprosy-and-leprosy-reactions-th17-immune-response-in-leprosy
#19
Márcio Bezerrra Santos, Daniela Teles de Oliveira, Rodrigo Anselmo Cazzaniga, Crisuelle Santana Varjão, Priscila Lima Dos Santos, Micheli L B Santos, Cristiane Bane Correia, Daniela R Faria, Marise do Vale Simon, João Santana Silva, Walderez O Dutra, Steven G Reed, Malcolm S Duthie, Roque Pahceco de Almeida, Amélia Ribeiro de Jesus
It is well established that helper T cell responses influence resistance or susceptibility to Mycobacterium leprae infection, but the role of more recently described helper T cell subsets in determining severity is less clear. To investigate the involvement of Th17 cells in the pathogenesis of leprosy, we determined the immune profile with variant presentations of leprosy. Firstly, IL-17A, IFN-γ and IL-10 were evaluated in conjunction with CD4(+) T cell staining by confocal microscopy of lesion biopsies from tuberculoid (TT) and lepromatous (LL) patients...
April 20, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28425862/the-impact-of-il-17-in-atherosclerosis
#20
Xinjie Lu
Atherosclerosis is a chronic vascular disease in which atherosclerotic plaques develop in the arterial wall. It is believed that inflammation plays a major role in atherosclerotic formation and progression. Thus, atherosclerosis can be considered as an inflammatory disease of the arterial vessel. Mouse model demonstrated that T and B cell deficiency reduces the atherosclerotic burden in the formation of an atherosclerotic lesion. CD4+ T helper cells (Th), such as Th1 cells known being the major CD4+ T cell subtype found in mouse models of atherogenesis, increase plaque formation caused by oxLDL...
April 19, 2017: Current Medicinal Chemistry
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