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https://www.readbyqxmd.com/read/28345650/rational-combination-of-oncolytic-vaccinia-virus-and-pd-l1-blockade-works-synergistically-to-enhance-therapeutic-efficacy
#1
Zuqiang Liu, Roshni Ravindranathan, Pawel Kalinski, Z Sheng Guo, David L Bartlett
Both anti-PD1/PD-L1 therapy and oncolytic virotherapy have demonstrated promise, yet have exhibited efficacy in only a small fraction of cancer patients. Here we hypothesized that an oncolytic poxvirus would attract T cells into the tumour, and induce PD-L1 expression in cancer and immune cells, leading to more susceptible targets for anti-PD-L1 immunotherapy. Our results demonstrate in colon and ovarian cancer models that an oncolytic vaccinia virus attracts effector T cells and induces PD-L1 expression on both cancer and immune cells in the tumour...
March 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28326171/large-scale-isolation-and-cytotoxicity-of-extracellular-vesicles-derived-from-activated-human-natural-killer-cells
#2
Ambrose Y Jong, Chun-Hua Wu, Jingbo Li, Jianping Sun, Muller Fabbri, Alan S Wayne, Robert C Seeger
Extracellular vesicles (EVs) have been the focus of great interest, as they appear to be involved in numerous important cellular processes. They deliver bioactive macromolecules such as proteins, lipids, and nucleic acids, allowing intercellular communication in multicellular organisms. EVs are secreted by all cell types, including immune cells such as natural killer cells (NK), and they may play important roles in the immune system. Currently, a large-scale procedure to obtain functional NK EVs is lacking, limiting their use clinically...
2017: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/28322863/deep-immune-profiling-by-mass-cytometry-links-human-t-and-nk-cell-differentiation-and-cytotoxic-molecule-expression-patterns
#3
Bertram Bengsch, Takuya Ohtani, Ramin Sedaghat Herati, Niels Bovenschen, Kyong-Mi Chang, E John Wherry
The elimination of infected or tumor cells by direct lysis is a key T and NK cell effector function. T and NK cells can kill target cells by coordinated secretion of cytotoxic granules containing one or both pore-forming proteins, perforin and granulysin and combinations of granzyme (Gzm) family effector proteases (in humans: Gzm A, B, K, M and H). Understanding the pattern of expression of cytotoxic molecules and the relationship to different states of T and NK cells may have direct relevance for immune responses in autoimmunity, infectious disease and cancer...
March 17, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/28317931/recruitment-of-bone-marrow-cd11b-gr-1-cells-by-polymeric-nanoparticles-for-antigen-cross-presentation
#4
Ya-Wun Yang, Wen-Hui Luo
The objective of this study was to investigate the function of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) on the activation of antigen-specific CD8(+) T cell responses via the CD11b(+)Gr(-)1(+) myeloid subpopulations in murine bone marrow (BM). PLGA NPs containing ovalbumin (OVA) were fabricated by the double-emulsion method. The CD11b(+)Gr-1(low)Ly-6C(high) and CD11b(+)Gr-1(high)Ly-6C(low) subsets from mice bone marrow were sorted and treated with the PLGA/OVA NPs, followed by co-culture with the carboxyfluorescein succinimidyl ester (CFSE)-labelled OT-I CD8(+) cells...
March 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28306665/molecular-mechanisms-that-mediate-invasion-and-egress-of-malaria-parasites-from-red-blood-cells
#5
Aditi Alaganan, Pallavi Singh, Chetan E Chitnis
PURPOSE OF REVIEW: Malaria parasites invade and multiply in diverse host cells during their complex life cycle. Some blood stage parasites transform into male and female gametocytes that are transmitted by female anopheline mosquitoes. The gametocytes are activated in the mosquito midgut to form male and female gametes, which egress from RBCs to mate and form a zygote. Here, we will review our current understanding of the molecular mechanisms that mediate invasion and egress by malaria parasites at different life cycle stages...
March 16, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28303727/enhancement-of-nk-cells-proliferation-and-function-by-shikonin
#6
Yan Li, Hailin Lu, Yongchun Gu, Zhiqiang Ning, Tinghua Cao, Chao Chen, Chengru Hu, Min Tao
CONTEXT: Shikonin is a kind of naphthoquinone compound found mainly in Lithospermum erythrorhizon Sieb,et Zucc. Previous studies have shown that Shikonin has anti-tumor, anti-inflammatory and extensive pharmacological effects. According to new studies, Shikonin could also modulate the immune system function, but the effect to NK (nature killer) cells is yet unknown. OBJECTIVE: To investigate the effect and mechanism of Shikonin on NK cells proliferation and cytotoxicity to colon cancer cell line (Caco-2)...
March 17, 2017: Immunopharmacology and Immunotoxicology
https://www.readbyqxmd.com/read/28296049/qsar-and-molecular-docking-studies-on-designing-inhibitors-of-the-perforin
#7
Fucheng Song, Lianhua Cui, Jinmei Piao, Hui Liang, Hongzong Si, Yunbo Duan, Honglin Zhai
Quantitative structure-activity relationship (QSAR) studies were performed on a series of 5-Arylidene-2thioxoimidazolidin-4-ones derivatives as the inhibitors of perforin, and to gain insights about the structural determinants for designing new drug molecules. The heuristic method (HM) could explore the descriptors responsible for bioactivity and gain a best linear model with R(2) 0.82. Gene expression programming (GEP) method generated a novel nonlinear function model with R(2) 0.92 for training set, and R(2) 0...
March 14, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28289860/the-pd-l1-pd-1-pathway-promotes-dysfunction-but-not-exhaustion-in-tumor-responding-t-cells-from-pleural-effusions-in-lung-cancer-patients
#8
Heriberto Prado-Garcia, Susana Romero-Garcia, Alejandra Puerto-Aquino, Uriel Rumbo-Nava
Malignant pleural effusions are frequent in patients with advanced stages of lung cancer and are commonly infiltrated by lymphocytes and tumor cells. CD8+ T cells from these effusions have reduced effector functions. The programmed death receptor 1(PD-1)/programmed death ligand 1 (PD-L1) pathway is involved in T-cell exhaustion, and it might be responsible for T-cell dysfunction in lung cancer patients. Here, we show that PD-L1 is expressed on tumor cell samples from malignant effusions, on lung cancer cell lines, and, interestingly, on MRC-5 lung fibroblasts...
March 13, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28282548/attenuated-in-vitro-effects-of-ifn-%C3%AE-il-2-and-il-12-on-functional-and-receptor-characteristics-of-peripheral-blood-lymphocytes-in-metastatic-melanoma-patients
#9
Katarina M Mirjačić Martinović, Ana M Vuletić, Nada Lj Babović, Radan R Džodić, Gordana M Konjević, Vladimir B Jurišić
Considering tumor-induced suppression of lymphocytes the aim of this study was to investigate in vitro effects of IFN-α, IL-2, IL-12 and IL-18 as immunomodulating agents on the functional and receptor characteristics of peripheral blood lymphocytes (PBL) in metastatic melanoma (MM) patients compared to healthy controls (HC). In HC IFN-α, IL-2 and IL-12 enhanced mRNA level of perforin by inducing pSTAT-1 and pSTAT-5 signaling molecules. Additionally, the expression of NKG2D activating receptor and its DAP10 signaling molecule was upregulated by IL-2...
March 7, 2017: Cytokine
https://www.readbyqxmd.com/read/28280496/cd4-ctl-a-cytotoxic-subset-of-cd4-t-cells-their-differentiation-and-function
#10
REVIEW
Arata Takeuchi, Takashi Saito
CD4(+) T cells with cytotoxic activity (CD4 CTL) have been observed in various immune responses. These cells are characterized by their ability to secrete granzyme B and perforin and to kill the target cells in an MHC class II-restricted fashion. Although CD4 CTLs were once thought to be an in vitro artifact associated with long-term culturing, they have since been identified in vivo and shown to play important roles in antiviral and antitumor immunity, as well as in inflammation. Functional characterization of CD4 CTL suggests their potential significance for therapeutic purposes...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28273905/nkg2d-modulates-aggravation-of-liver-inflammation-by-activating-nk-cells-in-hbv-infection
#11
Yadong Wang, Wei Wang, Chuan Shen, Yong Wang, Mingjing Jiao, Weiyan Yu, Hongzhu Yin, Xiaobo Shang, Qianfei Liang, Caiyan Zhao
Hepatitis B virus (HBV) infection is thought to be an immune-mediated liver disease. The mechanisms underlying natural killer (NK) cell group 2D receptor (NKG2D) that activates NK cells and participates in anti-HBV immunity and immunopathology has not been thoroughly elucidated. Peripheral NKG2D(+) and IFN-γ(+) NK cells frequencies and intrahepatic NKG2D and IFN-γ mRNA and protein expressions were determined in HBV-infected patients. Levels of NKG2D and IFN-γ mRNA and protein in NK cells, co-cultured with HBV-replicating HepG2 cells with or without NKG2D blockade, were analyzed...
December 2017: Scientific Reports
https://www.readbyqxmd.com/read/28270454/perforin-and-cd107a-testing-are-superior-to-nk-cell-function-testing-for-screening-patients-for-genetic-hlh
#12
Tamar S Rubin, Kejian Zhang, Carrie Gifford, Adam Lane, Jack J Bleesing, Rebecca A Marsh
Primary HLH (hemophagocytic lymphohistiocytosis) can be caused by bi-allelic mutations in PRF1, encoding perforin, or UNC13D, STXBP2, STX11, RAB27A, LYST and AP3B1, encoding proteins involved in cytotoxic lymphocyte degranulation. Natural killer (NK) cell cytotoxicity assays can quickly screen for all these genetic diseases, facilitating treatment, but combining NK cell perforin expression and CD107a upregulation tests can as well. To determine the relative diagnostic accuracies for each approach, we retrospectively reviewed screening test performance in 1614 patients referred for HLH evaluation...
March 7, 2017: Blood
https://www.readbyqxmd.com/read/28264905/perforin-expression-by-cd8-t-cells-is-sufficient-to-cause-fatal-brain-edema-during-experimental-cerebral-malaria
#13
Matthew Huggins, Holly L Johnson, Fang Jin, Aurelie N'Songo, Lisa M Hanson, Stephanie J LaFrance, Noah S Butler, John T Harty, Aaron J Johnson
Human cerebral malaria (HCM) is a serious complication of Plasmodium falciparum infection. The most severe outcomes for patients include coma, permanent neurological deficits, and death. Recently, a large-scale magnetic resonance imaging (MRI) study in humans identified brain swelling as the most prominent predictor of fatal HCM. Therefore, in this study we sought to define the mechanism controlling brain edema through the use of the murine experimental cerebral malaria (ECM) model. Specifically, we investigated the ability of CD8 T cells to initiate brain edema during ECM...
March 6, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28262554/target-expression-generation-preclinical-activity-and-pharmacokinetics-of-the-bcma-t-cell-bispecific-antibody-em801-for-multiple-myeloma-treatment
#14
Anja Seckinger, Jose Antonio Delgado, Samuel Moser, Laura Moreno, Brigitte Neuber, Anna Grab, Susanne Lipp, Juana Merino, Felipe Prosper, Martina Emde, Camille Delon, Melanie Latzko, Reto Gianotti, Remo Lüoend, Ramona Murr, Ralf J Hosse, Lydia Jasmin Harnisch, Marina Bacac, Tanja Fauti, Christian Klein, Aintzane Zabaleta, Jens Hillengass, Elisabetta Ada Cavalcanti-Adam, Anthony D Ho, Michael Hundemer, Jesus F San Miguel, Klaus Strein, Pablo Umaña, Dirk Hose, Bruno Paiva, Minh Diem Vu
We identified B cell maturation antigen (BCMA) as a potential therapeutic target in 778 newly diagnosed and relapsed myeloma patients. We constructed an IgG-based BCMA-T cell bispecific antibody (EM801) and showed that it increased CD3(+) T cell/myeloma cell crosslinking, followed by CD4(+)/CD8(+) T cell activation, and secretion of interferon-γ, granzyme B, and perforin. This effect is CD4 and CD8 T cell mediated. EM801 induced, at nanomolar concentrations, myeloma cell death by autologous T cells in 34 of 43 bone marrow aspirates, including those from high-risk patients and patients after multiple lines of treatment, tumor regression in six of nine mice in a myeloma xenograft model, and depletion of BCMA(+) cells in cynomolgus monkeys...
February 27, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28258194/antiparasitic-treatment-induces-an-improved-cd8-t-cell-response-in-chronic-chagasic-patients
#15
Jose Mateus, Elena Pérez-Antón, Paola Lasso, Adriana Egui, Nubia Roa, Bartolomé Carrilero, John M González, M Carmen Thomas, Concepción J Puerta, Manuel C López, Adriana Cuéllar
Chagas disease is a chronic infection caused by Trypanosoma cruzi, an intracellular protozoan parasite. Chronic chagasic patients (CCPs) have dysfunctional CD8(+) T cells that are characterized by impaired cytokine production, high coexpression of inhibitory receptors, and advanced cellular differentiation. Most patients diagnosed in the chronic phase of Chagas disease already exhibit heart involvement, and there is no vaccination that protects against the disease. Antiparasitic treatment is controversial as to its indication for this stage of the disease...
March 3, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28253869/reduced-prf1-enhancer-methylation-in-children-with-a-history-of-severe-rsv-bronchiolitis-in-infancy-an-association-study
#16
Magdeldin Elgizouli, Chad Logan, Ruth Grychtol, Dietrich Rothenbacher, Alexandra Nieters, Andrea Heinzmann
BACKGROUND: Acute lower respiratory tract infection is the commonest disease affecting children under five worldwide. Respiratory syncytial virus (RSV) is among the most common causative pathogens. Epidemiological data suggest an association between severe viral respiratory infections in infancy and increased incidence of childhood wheeze and asthma. DNA methylation is involved in immune cell differentiation and identity. It provides an avenue for environmental influences on the genome and therefore has potential as a marker for sustained effects of infectious insults...
March 3, 2017: BMC Pediatrics
https://www.readbyqxmd.com/read/28251796/cytotoxicity-of-natural-killer-cells-activated-through-nkg2d-contributes-to-the-development-of-bronchiolitis-obliterans-in-a-murine-heterotopic-tracheal-transplant-model
#17
Toru Kawakami, Koyu Ito, Yasushi Matsuda, Masahumi Noda, Akira Sakurada, Yasushi Hoshikawa, Yoshinori Okada, Kouetsu Ogasawara
Bronchiolitis obliterans after lung transplantation is a major cause of postoperative mortality in which T cell-mediated immunity is known to play an important role. However, the exact contribution of NK cells, which have similar functions to CD8(+) T cells, has not been defined. Here, we assessed the role of NK cells in murine bronchiolitis obliterans through heterotopic tracheal transplantations and found a greater percentage of NK cells in allografts than in isografts. Depletion of NK cells using an anti-NK1...
March 1, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28251711/trophoblasts-regulate-natural-killer-cells-via-control-of-interleukin-15-receptor-signaling
#18
Seo Y Park, Sohyun Yun, Byung J Ryu, Ae R Han, Sung K Lee
PROBLEM: Trophoblasts are known to decrease natural killer (NK) cell cytotoxicity. However, little is known about the interaction between trophoblasts and NK cells during pregnancy. Interleukin-15 (IL-15) is essential for priming NK cells and maximizing their effector functions. We investigated whether trophoblasts regulate NK cell activation via IL-15/IL-2 receptor and its signaling pathways. METHOD OF STUDY: Natural killer-92 cells were primed with human first-trimester trophoblast cells (Sw...
March 2, 2017: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/28248832/pathophysiology-of-pediatric-multiple-organ-dysfunction-syndrome
#19
Joseph A Carcillo, Bradley Podd, Rajesh Aneja, Scott L Weiss, Mark W Hall, Timothy T Cornell, Thomas P Shanley, Lesley A Doughty, Trung C Nguyen
OBJECTIVE: To describe the pathophysiology associated with multiple organ dysfunction syndrome in children. DATA SOURCES: Literature review, research data, and expert opinion. STUDY SELECTION: Not applicable. DATA EXTRACTION: Moderated by an experienced expert from the field, pathophysiologic processes associated with multiple organ dysfunction syndrome in children were described, discussed, and debated with a focus on identifying knowledge gaps and research priorities...
March 2017: Pediatric Critical Care Medicine
https://www.readbyqxmd.com/read/28248119/familial-hemophagocytic-lymphohistiocytosis-from-autopsy-to-prenatal-diagnosis-report-of-a%C3%A2-case
#20
Marta Ježová, Renata Gaillyová
Hemophagocytic lymphohistiocytosis is a rare immunologic disorder affecting small children. It is characterized by an excessive and injurious immune response which turns rapidly fatal unless promptly and effectively treated. The main clinical signs are prolonged fever, hepatosplenomegaly, bleeding and laboratory findings of pancytopenia, increased serum transaminases, hypertriglyceridemia and hypofibrinogenemia. Four genes responsible for familiar hemophagocytic lymphohistiocytosis, which is inherited in autosomal recessive manner, have been identified so far...
2017: Ceskoslovenská Patologie
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