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PD-1 B cell

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https://www.readbyqxmd.com/read/28912267/antitumor-immunity-is-defective-in-t-cell-specific-microrna-155-deficient-mice-and-is-rescued-by-immune-checkpoint-blockade
#1
Thomas B Huffaker, Soh-Hyun Lee, William W Tang, Jared A Wallace, Margaret Alexander, Marah C Runtsch, Dane K Larsen, Jacob Thompson, Andrew G Ramstead, Warren P Voth, Ruozhen Hu, June L Round, Matthew A Williams, Ryan M O'Connell
MicroRNA-155 (miR-155) regulates antitumor immune responses. However, its specific functions within distinct immune cell types have not been delineated in conditional knockout (KO) mouse models. In this study, we investigated the role of miR-155 specifically within T cells during the immune response to syngeneic tumors. We found that miR-155 expression within T cells is required to limit syngeneic tumor growth and promote interferon gamma (IFNγ) production by T cells within the tumor microenvironment. Consequently, we found that miR-155 expression by T cells is necessary for proper tumor-associated macrophage (TAM) expression of IFNγ-inducible genes...
September 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28899983/regulatory-nk-cells-mediated-between-immunosuppressive-monocytes-and-dysfunctional-t-cells-in-chronic-hbv-infection
#2
Haijun Li, Naicui Zhai, Zhongfeng Wang, Hongxiao Song, Yang Yang, An Cui, Tianyang Li, Guangyi Wang, Junqi Niu, Ian Nicholas Crispe, Lishan Su, Zhengkun Tu
BACKGROUND AND AIMS: HBV infection represents a major health problem worldwide, but the immunological mechanisms by which HBV causes chronic persistent infection remain only partly understood. Recently, cell subsets with suppressive features have been recognised among monocytes and natural killer (NK) cells. Here we examine the effects of HBV on monocytes and NK cells. METHODS: Monocytes and NK cells derived from chronic HBV-infected patients and healthy controls were purified and characterised for phenotype, gene expression and cytokines secretion by flow cytometry, quantitative real-time (qRT)-PCR, ELISA and western blotting...
September 12, 2017: Gut
https://www.readbyqxmd.com/read/28891906/first-in-human-treatment-with-a-dendritic-cell-targeting-lentiviral-vector-expressing-ny-eso-1-lv305-induces-deep-durable-response-in-refractory-metastatic-synovial-sarcoma-patient
#3
Seth M Pollack, Hailing Lu, Sacha Gnjatic, Neeta Somaiah, Ryan B O'Malley, Robin L Jones, Frank J Hsu, Jan Ter Meulen
Effective induction of antitumor T cells is a pivotal goal of cancer immunotherapy. To this end, lentiviral vectors (LV) are uniquely poised to directly prime CD8 T-cell responses via transduction of dendritic cells in vivo and have shown promise as active cancer therapeutics in preclinical tumor models. However, until now, significant barriers related to production and regulation have prevented their widespread use in the clinic. We developed LV305, a dendritic cell-targeting, integration-deficient, replication incompetent LV from the ZVex platform, encoding the full-length cancer-testis antigen NY-ESO-1...
October 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28887367/tfr-cells-lack-il-2r%C3%AE-but-express-decoy-il-1r2-and-il-1ra-and-suppress-the-il-1-dependent-activation-of-tfh-cells
#4
Paul-Gydeon G Ritvo, Guillame Churlaud, Valentin Quiniou, Laura Florez, Faustine Brimaud, Gwladys Fourcade, Encarnita Mariotti-Ferrandiz, David Klatzmann
Follicular regulatory T (Tfr) cells from lymph node germinal centers control follicular helper T (Tfh) cell-dependent B cell activation. These scarce cells, often described and purified as CD25(+) cells, are thought to be derived from thymic regulatory T (Treg) cells. However, we observed that mouse Tfr cells do not respond to interleukin-2 (IL-2), unlike Treg cells. Stringent immunophenotyping based on B cell lymphoma 6 (Bcl6), programmed cell death protein 1 (PD-1), and CXCR5 expression revealed that Tfr cells are actually CD25(-), in mice and humans...
September 8, 2017: Science Immunology
https://www.readbyqxmd.com/read/28886376/converting-cold-into-hot-tumors-by-combining-immunotherapies
#5
John B A G Haanen
In a small phase Ib study in this issue of Cell, Ribas et al. report that the combination of intralesional injection of a modified human herpes simplex virus and systemic anti-PD-1 treatment resulted in a 62% response rate in patients with metastatic melanoma, accompanied by enhanced T cell infiltration in virus-injected lesions.
September 7, 2017: Cell
https://www.readbyqxmd.com/read/28883511/cytotoxic-response-against-epstein-barr-virus-coexists-with-diffuse-large-b-cell-lymphoma-tolerogenic-microenvironment-clinical-features-and-survival-impact
#6
Melina Cohen, Aldana G Vistarop, Fuad Huaman, Marina Narbaitz, Fernanda Metrebian, Elena De Matteo, María V Preciado, Paola A Chabay
Epstein-Barr Virus (EBV) is present in neoplastic cells of 15% of Asian and Latin-American diffuse large B-cell lymphoma (DLBCL) patients. Even though a tolerogenic microenvironment was recently described in DLBCL, little is known concerning immunomodulatory features induced by EBV. As suggested in Hodgkin lymphoma, EBV-specific cytotoxic T-cells are increased but showing immune exhaustion features. Hence, host immunity suppression may play a critical role in tumor progression. This study aimed to investigate, whether an association between tumor microenvironment features and EBV presence is taking place, and its clinical correlate...
September 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28883281/novel-mechanism-of-immune-evasion-in-cancer-via-structural-variations-of-the-pd-l1-gene
#7
Seishi Ogawa
Cancer cells are thought to circumvent immune surveillance through PD-1/PD-L1 signaling. However, the genetic basis for PD-L1-PD-L1-mediated immune escape has not been completely understood, with the exception of elevated PD-L1 expression by gene amplification and the utilization of an ectopic promoter by translocation. Recently, we demonstrated a unique genetic mechanism of immune escape caused by structural variations (SVs) commonly disrupting the 3' part of the PD-L1 gene. These SVs invariably cause a marked elevation of aberrant PD-L1 transcripts that are stabilized by truncation of the 3'-untranslated region (UTR), and thereby widely affect multiple common cancer types, including adult T-cell leukemia/lymphoma (27%), diffuse large B-cell lymphoma (8%), and adenocarcinoma of the stomach (2%)...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28875836/coinhibitory-molecule-pd-1-as-a-therapeutic-target-in-the-microenvironment-of-multiple-myeloma
#8
Djordje Atanackovic, Tim Luetkens, Mary Steinbach, Nicolaus Kröger
Immunological dysfunction in the microenvironment of multiple myeloma is a potential target for immune-mediated therapies. The programmed death 1 (PD-1) receptor is expressed on the surface of exhausted T and B cells and its ligand PD-L1 is expressed on tumor cells and inhibits T-cell-mediated apoptosis. Inhibiting such "checkpoint" by monoclonal antibodies recently has been shown high activity in solid tumors and malignant lymphomas. In patients with multiple myeloma PD-L1 is overexpressed on myeloma cells and PD1 on T-cells suggesting an active role of PD- 1/PD-L1 in the immunosuppressive microenvironment...
September 6, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28874354/the-inhibitory-signaling-receptor-protocadherin-18-regulates-tumor-infiltrating-cd8-t-cell-function
#9
Alan B Frey
Cancers are infiltrated with antitumor CD8+ T cells that arise during tumor growth, but are defective in effector phase functions because of the suppressive microenvironment. The reactivation of TILs can result in tumor destruction, showing that lytic dysfunction in CD8+ tumor-infiltrating lymphocytes (TILs) permits tumor growth. Like all memory T cells, TILs express inhibitory signaling receptors (aka checkpoint inhibitor molecules) that downregulate TCR-mediated signal transduction upon TIL interaction with cells expressing cognate ligands, thereby restricting cell activation and preventing the effector phase...
September 5, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28870600/interleukin-10-enhanced-cd8-t-cell-activity-and-reduced-cd8-t-cell-apoptosis-in-patients-with-diffuse-large-b-cell-lymphoma
#10
Huiying Qiu, Xiaoxia Hu, Lei Gao, Li Chen, Jie Chen, Joanna Yuan, Chongmei Huang, Xiaoqian Xu, Jianmin Yang
The pleiotropic cytokine interleukin (IL)-10 is best characterized by its ability to downregulate inflammation and promote peripheral tolerance. On the other hand, IL-10 was also found to maintain the effector response of CD8(+) T cells and promote the expansion of tumor-resident CD8(+) T cells. In diffuse large B cell lymphoma (DLBCL), the role of IL-10 has been characterized in tumor cells but not in CD8(+) T cells. We found that CD8(+) T cells in DLBCL presented robust interferon (IFN)-γ expression early during TCR-activation but could not maintain this response later on, which was characterized by significantly lower CD8(+) T cell degranulation and higher apoptosis...
September 1, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28866823/neuroprotective-effects-of-baicalein-on-acrolein-induced-neurotoxicity-in-the-nigrostriatal-dopaminergic-system-of-rat-brain
#11
Wei-Zhong Zhao, Hsiang-Tsui Wang, Hui-Ju Huang, Yu-Li Lo, Anya Maan-Yuh Lin
Elevated levels of acrolein, an α,β-unsaturated aldehyde are detected in the brain of patients with Parkinson's disease (PD). In the present study, the neuroprotective effect of baicalein (a phenolic flavonoid in the dried root of Scutellaria baicalensis Georgi) on acrolein-induced neurodegeneration of nigrostriatal dopaminergic system was investigated using local infusion of acrolein in the substantia nigra (SN) of rat brain. Systemic administration of baicalein (30 mg/kg, i.p.) significantly attenuated acrolein-induced elevations in 4-hydroxy-2-noneal (a product of lipid peroxidation), N-(3-formyl-3,4-dehydropiperidino)lysine (a biomarker of acrolein-conjugated proteins), and heme-oxygenase-1 levels (a redox-regulated protein) in the infused SN, indicating that baicalein inhibited acrolein-induced oxidative stress and protein conjugation...
September 2, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28864814/rituximab-based-first-line-treatment-for-chronic-gvhd-after-allogeneic-sct-results-of-a-phase-2-study
#12
Florent Malard, Myriam Labopin, Ibrahim Yakoub-Agha, Sylvain Chantepie, Thierry Guillaume, Didier Blaise, Reza Tabrizi, Leonardo Magro, Bernard Vanhove, Gilles Blancho, Philippe Moreau, Béatrice Gaugler, Patrice Chevallier, Mohamad Mohty
Chronic graft-versus-host disease (cGVHD) is the main cause of late non-relapse mortality and morbidity after allogeneic stem-cell transplantation (allo-SCT). In order to improve such patients' outcome, we conducted a phase 2, prospective, multicenter trial to test the efficacy of addition of rituximab to corticosteroid and cyclosporine A as first line therapy for newly diagnosed cGVHD after allo-SCT. Twenty-four patients (median age, 47 years) with mild (n=2), moderate (n=7) or severe (n=15) cGVHD were included...
September 1, 2017: Blood
https://www.readbyqxmd.com/read/28861871/combinatorial-therapies-in-melanoma-mapk-inhibitors-and-beyond
#13
REVIEW
Alice Y Zhou, Douglas B Johnson
Melanoma is the most aggressive of the skin cancers, with historically high rates of morbidity and mortality due to its resistance to traditional cytotoxic therapies. Recently, however, breakthroughs in new therapies have dramatically changed clinical outcomes of this disease. These advances emerged from an improved understanding of tumor oncogenesis and the interacting tumor microenvironment. Small molecules that target the oncogenic mitogen-activated protein kinase (MAPK) pathway, specifically the tyrosine kinase BRAF and its downstream signaling partner MEK, have demonstrated an improved overall survival and progression-free survival for BRAF-mutant melanoma...
August 31, 2017: American Journal of Clinical Dermatology
https://www.readbyqxmd.com/read/28858473/molecular-targeted-immunotherapeutic-strategy-for-melanoma-via-dual-targeting-nanoparticles-delivering-small-interfering-rna-to-tumor-associated-macrophages
#14
Yuan Qian, Sha Qiao, Yanfeng Dai, Guoqiang Xu, Bolei Dai, Lisen Lu, Xiang Yu, Qingming Luo, Zhihong Zhang
Tumor-associated macrophages (TAMs) are a promising therapeutic target for cancer immunotherapy. Targeted delivery of therapeutic drugs to the tumor-promoting M2-like TAMs is challenging. Here, we developed M2-like TAM dual-targeting nanoparticles (M2NPs), whose structure and function were controlled by α-peptide (a scavenger receptor B type 1 (SR-B1) targeting peptide) linked with M2pep (an M2 macrophage binding peptide). By loading anti-colony stimulating factor-1 receptor (anti-CSF-1R) small interfering RNA (siRNA) on the M2NPs, we developed a molecular-targeted immunotherapeutic approach to specifically block the survival signal of M2-like TAMs and deplete them from melanoma tumors...
September 6, 2017: ACS Nano
https://www.readbyqxmd.com/read/28856541/glycoprotein-nmb-an-emerging-role-in-neurodegenerative-disease
#15
REVIEW
Kevin M Budge, Matthew L Neal, Jason R Richardson, Fayez F Safadi
Neurodegeneration is characterized by severe neuronal loss leading to the cognitive and physical impairments that define various neurodegenerative diseases. Neuroinflammation is one hallmark of neurodegenerative diseases and can ultimately contribute to disease progression. Increased inflammatory cytokines, such as interleukin-6 (IL-6), interleukin-1β (IL-1 β), and tumor necrosis factor-α (TNF-α) are associated with Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS)...
August 30, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28854942/the-biology-of-hepatocellular-carcinoma-implications-for-genomic-and-immune-therapies
#16
REVIEW
Galina Khemlina, Sadakatsu Ikeda, Razelle Kurzrock
Hepatocellular carcinoma (HCC), the most common type of primary liver cancer, is a leading cause of cancer-related death worldwide. It is highly refractory to most systemic therapies. Recently, significant progress has been made in uncovering genomic alterations in HCC, including potentially targetable aberrations. The most common molecular anomalies in this malignancy are mutations in the TERT promoter, TP53, CTNNB1, AXIN1, ARID1A, CDKN2A and CCND1 genes. PTEN loss at the protein level is also frequent. Genomic portfolios stratify by risk factors as follows: (i) CTNNB1 with alcoholic cirrhosis; and (ii) TP53 with hepatitis B virus-induced cirrhosis...
August 30, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28851824/blockade-of-surface-bound-tgf-%C3%AE-on-regulatory-t-cells-abrogates-suppression-of-effector-t-cell-function-in-the-tumor-microenvironment
#17
Sadna Budhu, David A Schaer, Yongbiao Li, Ricardo Toledo-Crow, Katherine Panageas, Xia Yang, Hong Zhong, Alan N Houghton, Samuel C Silverstein, Taha Merghoub, Jedd D Wolchok
Regulatory T cells (Tregs) suppress antitumor immunity by inhibiting the killing of tumor cells by antigen-specific CD8(+) T cells. To better understand the mechanisms involved, we used ex vivo three-dimensional collagen-fibrin gel cultures of dissociated B16 melanoma tumors. This system recapitulated the in vivo suppression of antimelanoma immunity, rendering the dissociated tumor cells resistant to killing by cocultured activated, antigen-specific T cells. Immunosuppression was not observed when tumors excised from Treg-depleted mice were cultured in this system...
August 29, 2017: Science Signaling
https://www.readbyqxmd.com/read/28851562/viral-load-affects-the-immune-response-to-hbv-in-mice-with-humanized-immune-system-and-liver
#18
Mathilde Dusséaux, Guillemette Masse-Ranson, Sylvie Darche, James Ahodantin, Yan Li, Oriane Fiquet, Elodie Beaumont, Pierrick Moreau, Lise Rivière, Christine Neuveut, Patrick Soussan, Philippe Roingeard, Dina Kremsdorf, James P Di Santo, Helene Strick-Marchand
BACKGROUND & AIMS: Hepatitis B virus (HBV) infects hepatocytes, but the mechanisms of the immune response against the virus, and how it affects disease progression, are unclear. METHODS: We performed studies with BALB/c Rag2(-/-)Il2rg(-/-)Sirpa(NOD)Alb-uPA(tg/tg) mice, stably engrafted with human hepatocytes (HUHEP) with or without a human immune system (HIS). HUHEP and HIS-HUHEP mice were given an intraperitoneal injection of HBV. Mononuclear cells were isolated from spleen and liver for analysis by flow cytometry...
August 26, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28847007/homeostatic-control-of-metabolic-and-functional-fitness-of-treg-cells-by-lkb1-signalling
#19
Kai Yang, Daniel Bastardo Blanco, Geoffrey Neale, Peter Vogel, Julian Avila, Clary B Clish, Chuan Wu, Sharad Shrestha, Sherri Rankin, Lingyun Long, Anil Kc, Hongbo Chi
Regulatory T cells (Treg cells) have a pivotal role in the establishment and maintenance of immunological self-tolerance and homeostasis. Transcriptional programming of regulatory mechanisms facilitates the functional activation of Treg cells in the prevention of diverse types of inflammatory responses. It remains unclear how Treg cells orchestrate their homeostasis and interplay with environmental signals. Here we show that liver kinase B1 (LKB1) programs the metabolic and functional fitness of Treg cells in the control of immune tolerance and homeostasis...
August 31, 2017: Nature
https://www.readbyqxmd.com/read/28840016/lung-adenocarcinoma-from-molecular-basis-to-genome-guided-therapy-and-immunotherapy
#20
REVIEW
Roberto Chalela, Víctor Curull, César Enríquez, Lara Pijuan, Beatriz Bellosillo, Joaquim Gea
Although adenocarcinoma (ADC) is the most frequent lung cancer, its diagnosis is often late, when the local invasion is important and/or the metastases have already appeared. Therefore, the mortality at 5 years is still very high, ranging from 51% to 99%, depending on the stage. The implementation of different molecular techniques has allowed genomic studies even in relatively small histological samples such as obtained with non-invasive or minimally invasive techniques, facilitating a better phenotyping of lung ADC...
July 2017: Journal of Thoracic Disease
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