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https://www.readbyqxmd.com/read/28651074/chimeric-antigen-receptor-engineered-natural-killer-and-natural-killer-t-cells-for-cancer-immunotherapy
#1
REVIEW
Dominique Bollino, Tonya J Webb
Natural killer (NK) cells of the innate immune system and NK T (NKT) cells, which have roles in both the innate and adaptive responses, are unique lymphocyte subsets that have similarities in their functions and phenotypes. Both cell types can rapidly respond to the presence of tumor cells and participate in immune surveillance and antitumor immune responses. This has incited interest in the development of novel cancer therapeutics based on NK and NKT cell manipulation. Chimeric antigen receptors (CARs), generated through the fusion of an antigen-binding region of a monoclonal antibody or other ligand to intracellular signaling domains, can enhance lymphocyte targeting and activation toward diverse malignancies...
June 9, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28650939/cd1d-restricted-natural-killer-t-cells-are-preserved-in-indian-long-term-nonprogressors
#2
Dharmendra Singh, Manisha Ghate, Sheela Godbole, Smita Kulkarni, Madhuri Thakar
BACKGROUND: Natural killer T (NKT) cells act as a bridge between innate and adaptive immune responses. Limited information is available regarding the role of NKT cells in the HIV disease progression especially HIV-1 C infection. METHODOLOGY: NKT cells were characterized for their frequency and the activation, aging, exhaustion status, and their proliferation ability in 32 long-term nonprogressors (LTNPs), 40 progressors, 18 patients before and after suppressive combination antiretroviral therapy (cART) along with 35 HIV-1-negative subjects using multicolor flow cytometry...
August 1, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28650455/clinical-impact-of-nk-cell-reconstitution-after-reduced-intensity-conditioned-unrelated-cord-blood-transplantation-in-patients-with-acute-myeloid-leukemia-analysis-of-a-prospective-phase-ii-multicenter-trial-on-behalf-of-the-soci%C3%A3-t%C3%A3-fran%C3%A3-aise-de-greffe-de
#3
S Nguyen, A Achour, L Souchet, S Vigouroux, P Chevallier, S Furst, A Sirvent, J-O Bay, G Socié, P Ceballos, A Huynh, J Cornillon, S Francois, F Legrand, I Yakoub-Agha, G Michel, N Maillard, G Margueritte, S Maury, M Uzunov, C-E Bulabois, M Michallet, L Clement, C Dauriac, K Bilger, J Lejeune, V Béziat, V Rocha, B Rio, S Chevret, V Vieillard
Unrelated cord blood transplantation (UCBT) after a reduced intensity conditioning regimen (RIC) has extended the use of UCB in elderly patients and those with co-morbidities without an HLA-identical donor, although post-transplant relapse remains a concern in high-risk acute myeloid leukemia (AML) patients. HLA incompatibilities between donor and recipient might enhance the alloreactivity of natural killer (NK) cells after allogeneic hematopoietic stem-cell transplantation (HSCT). We studied the reconstitution of NK cells and KIR-L mismatch in 54 patients who underwent a RIC-UCBT for AML in CR in a prospective phase II clinical trial...
June 26, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28649246/redirected-primary-human-chimeric-antigen-receptor-natural-killer-cells-as-an-off-the-shelf-immunotherapy-for-improvement-in-cancer-treatment
#4
REVIEW
Olaf Oberschmidt, Stephan Kloess, Ulrike Koehl
Primary human natural killer (NK) cells recognize and subsequently eliminate virus infected cells, tumor cells, or other aberrant cells. However, cancer cells are able to develop tumor immune escape mechanisms to undermine this immune control. To overcome this obstacle, NK cells can be genetically modified to express chimeric antigen receptors (CARs) in order to improve specific recognition of cancer surface markers (e.g., CD19, CD20, and ErbB2). After target recognition, intracellular CAR domain signaling (CD3ζ, CD28, 4-1BB, and 2B4) leads to activation of PI3K or DNAX proteins (DAP10, DAP12) and finally to enhanced cytotoxicity, proliferation, and/or interferon γ release...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28649243/distinct-blood-and-visceral-adipose-tissue-regulatory-t-cell-and-innate-lymphocyte-profiles-characterize-obesity-and-colorectal-cancer
#5
Gloria Donninelli, Manuela Del Cornò, Marina Pierdominici, Beatrice Scazzocchio, Rosaria Varì, Barbara Varano, Ilenia Pacella, Silvia Piconese, Vincenzo Barnaba, Massimo D'Archivio, Roberta Masella, Lucia Conti, Sandra Gessani
Visceral adipose tissue (VAT) is a main site where metabolic and immunologic processes interplay to regulate, at local and systemic level, the inflammatory status and immune response. Obesity-associated inflammation and immune dysfunctions are inextricably linked to tumor but, in spite of intense efforts, the mechanisms underpinning this association remain elusive. In this report, we characterized the profile of VAT-associated and circulating innate lymphocyte and regulatory T (Treg) cell subsets underlying inflammatory conditions, such as obesity and colorectal cancer (CRC)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28648866/cytokines-in-immunogenic-cell-death-applications-for-cancer-immunotherapy
#6
REVIEW
Anne Showalter, Arati Limaye, Jeremiah L Oyer, Robert Igarashi, Christina Kittipatarin, Alicja J Copik, Annette R Khaled
Despite advances in treatments like chemotherapy and radiotherapy, metastatic cancer remains a leading cause of death for cancer patients. While many chemotherapeutic agents can efficiently eliminate cancer cells, long-term protection against cancer is not achieved and many patients experience cancer recurrence. Mobilizing and stimulating the immune system against tumor cells is one of the most effective ways to protect against cancers that recur and/or metastasize. Activated tumor specific cytotoxic T lymphocytes (CTLs) can seek out and destroy metastatic tumor cells and reduce tumor lesions...
June 22, 2017: Cytokine
https://www.readbyqxmd.com/read/28647398/immune-modulatory-effects-of-syncytiotrophoblast-extracellular-vesicles-in-pregnancy-and-preeclampsia
#7
Claudia Göhner, Torsten Plösch, Marijke M Faas
Unique immunologic adaptations exist to successfully establish and maintain pregnancy and to avoid an immune attack against the semi allogenic fetus. These adaptations occur both locally at the maternofetal interface and in the peripheral circulation and affect the innate as well as the adaptive immune system. Pregnancy is characterized by a general inflammatory state with activation of monocytes and granulocytes, but also with suppressive lymphocytes (regulatory T cells), and skewing towards T helper 2 immunity...
June 7, 2017: Placenta
https://www.readbyqxmd.com/read/28646487/immunotoxic-effects-of-thymus-in-mice-following-exposure-to-nanoparticulate-tio2
#8
Fashui Hong, Yaoming Zhou, Yingjun Zhou, Ling Wang
Titanium dioxide nanoparticles (TiO2 NPs) have been extensively used in industry, medicine, and daily life, and have shown potential toxic effects for animals or humans. We noted that the effects of TiO2 NPs on the immune system and its mechanism of action in animals or humans have not been elucidated. Thus, mice were exposed to the TiO2 NPs (0, 1.25, 2.5, or 5 mg kg(-1) body weight) for 9 consecutive months. Exposure to TiO2 NPs was accumulated in the thymus, leading to a decrease in body weight and increases in the weight of the thymus or thymus indices...
June 24, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/28645775/altered-populations-of-natural-killer-cells-cytotoxic-t-lymphocytes-and-regulatory-t-cells-in-major-depressive-disorder-association-with-sleep-disturbance
#9
Hideo Suzuki, Jonathan Savitz, T Kent Teague, Siva K Gandhapudi, Chibing Tan, Masaya Misaki, Brett A McKinney, Michael R Irwin, Wayne C Drevets, Jerzy Bodurka
A subset of individuals with major depressive disorder (MDD) have impaired adaptive immunity characterized by a greater vulnerability to viral infection and a deficient response to vaccination along with a decrease in the number and/or activity of T cells and natural killer cells (NKC). Nevertheless, it remains unclear which specific subsets of lymphocytes are altered in MDD, a shortcoming we address here by utilizing an advanced fluorescence-activated cell sorting (FACS) method that allows for the differentiation of important functionally-distinct lymphocyte sub-populations...
June 20, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28644973/il-18-il-15-il-12-synergy-induces-elevated-and-prolonged-ifn-%C3%AE-production-by-ex-vivo-expanded-nk-cells-which-is-not-due-to-enhanced-stat4-activation
#10
Evan Lusty, Sophie M Poznanski, Karen Kwofie, Talveer S Mandur, Dean A Lee, Carl D Richards, Ali A Ashkar
The synergistic effect of IL-18/IL-15/IL-12 stimulation potently activates NK cells, inducing high levels of IFN-γ production. As a result of this potent stimulatory effect, NK cell pre-activation with IL-18/IL-15/IL-12 is being developed as a cancer immunotherapy. Ex vivo expansion of NK cells enables the efficient generation of large numbers of NK cells for wide-scale and repeated therapeutic use, and is thus an important source of NK cells for clinical application. However, the effects of IL-18/IL-15/IL-12 stimulation on ex vivo expanded NK cells have not yet been assessed...
June 20, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28644756/immunological-effects-of-hypomethylating-agents
#11
Katherine E Lindblad, Meghali Goswami, Christopher S Hourigan, Karolyn A Oetjen
Epigenetic changes resulting from aberrant methylation patterns are a recurrent observation in hematologic malignancies. Hypomethylating agents have a well-established role in the management of patients with high-risk myelodysplastic syndrome or acute myeloid leukemia. In addition to the direct effects of hypomethylating agents on cancer cells, there are several lines of evidence indicating a role for immune-mediated anti-tumor benefits from hypomethylating therapy. Areas Covered: We reviewed the clinical and basic science literature for the effects of hypomethylating agents, including the most commonly utilized therapeutics azacitidine and decitabine, on immune cell subsets...
June 23, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28643847/ncr1-deficiency-diminishes-the-generation-of-protective-murine-cytomegalovirus-antibodies-by-limiting-follicular-helper-t-cell-maturation
#12
Antonija Miletic, Maja Lenartic, Branka Popovic, Ilija Brizic, Tihana Trsan, Karmela Miklic, Ofer Mandelboim, Astrid Krmpotic, Stipan Jonjic
NKp46/NCR1 is an activating NK-cell receptor implicated in the control of various viral and bacterial infections. Recent findings also suggest that it plays a role in shaping the adaptive immune response to pathogens. Using NCR1-deficient (NCR1(gfp/gfp) ) mice we provide evidence for the role of NCR1 in antibody response to mouse cytomegalovirus infection (MCMV). The absence of NCR1 resulted in impaired maturation, function and NK-cell migration to regional lymph nodes. In addition, CD4(+) T-cell activation and follicular helper T-cell (Tfh) generation were reduced, leading to inferior germinal center (GC) B-cell maturation...
June 23, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28642882/tumor-related-exosomes-contribute-to-tumor-promoting-microenvironment-an-immunological-perspective
#13
REVIEW
Wuzhen Chen, Jingxin Jiang, Wenjie Xia, Jian Huang
Exosomes are a kind of cell-released membrane-form structures which contain proteins, lipids, and nucleic acids. These vesicular organelles play a key role in intercellular communication. Numerous experiments demonstrated that tumor-related exosomes (TEXs) can induce immune surveillance in the microenvironment in vivo and in vitro. They can interfere with the maturation of DC cells, impair NK cell activation, induce myeloid-derived suppressor cells, and educate macrophages into protumor phenotype. They can also selectively induce effector T cell apoptosis via Fas/FasL interaction and enhance regulatory T cell proliferation and function by releasing TGF-β...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28642148/biological-activity-of-glatiramer-acetate-on-treg-and-anti-inflammatory-monocytes-persists-for-more-than-10years-in-responder-multiple-sclerosis-patients
#14
Michela Spadaro, Francesca Montarolo, Simona Perga, Serena Martire, Federica Brescia, Simona Malucchi, Antonio Bertolotto
Glatiramer acetate (GA) is a widely used treatment for multiple sclerosis (MS), with incompletely defined mechanism of action. Short-term studies suggested its involvement in the modulation of anti-inflammatory cytokines and regulatory T cells (Treg), while long-term effect is still unknown. To investigate this aspect, we analyzed by flow-cytometry peripheral-blood Treg, natural killer (NK), CD4 and CD8 T-cells and anti-inflammatory CD14(+)CD163(+) monocytes from 37 healthy donor and 90 RRMS patients divided in untreated, treated with GA for 12months and from 34 to 192months...
June 19, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28639485/increased-shisa3-expression-characterizes-chronic-lymphocytic-leukemia-patients-sensitive-to-lenalidomide
#15
Rossana Maffei, Stefania Fiorcari, Silvia Martinelli, Stefania Benatti, Jenny Bulgarelli, Lara Rizzotto, Giulia Debbia, Rita Santachiara, Gian Matteo Rigolin, Francesco Forconi, Davide Rossi, Luca Laurenti, Giuseppe A Palumbo, Daniele Vallisa, Antonio Cuneo, Gianluca Gaidano, Mario Luppi, Roberto Marasca
Lenalidomide is a therapeutically effective drug in chronic lymphocytic leukemia (CLL). Twenty-seven CLL patients were treated with lenalidomide in a phase II clinical trial. Ten patients were grouped as responders (R) and 6 as nonresponders (NR). We evaluated T lymphocytes, NK, monocytes and dendritic cells at baseline and after treatment. A gene expression analysis was performed on 16 CLL samples collected before treatment. The levels of immune cells or immune-related cytokines are not different between R and NR patients...
June 22, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28639033/functional-restoration-of-cd56-bright-nk-cells-facilitates-immune-control-via-il-15-and-nkg2d-in-patients-under-antiviral-treatment-for-chronic-hepatitis-b
#16
Tao Chen, Lin Zhu, Aichao Shi, Lin Ding, Xiaoping Zhang, Zhenmin Tan, Wei Guo, Weiming Yan, Meifang Han, Jidong Jia, Xiaoping Luo, Detlef Schuppan, Qin Ning
BACKGROUND AND AIMS: Hepatitis B virus (HBV) is intrinsically immunogenic, with long-lasting immune control in many patients. However, the mechanisms and key cell types underlying effective immune control are incompletely understood. METHODS: We studied the restoration of natural killer (NK) cell numbers and function post antiviral treatment in 52 hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients who received telbivudine (LdT) for 48 weeks...
June 20, 2017: Hepatology International
https://www.readbyqxmd.com/read/28638738/activation-of-the-fcgammareceptoriiia-on-human-natural-killer-cells-leads-to-increased-expression-of-functional-interleukin-21-receptor
#17
Elizabeth L McMichael, Nicholas B Courtney, Megan C Duggan, Robert Wesolowski, Dionisia Quiroga, Sri Vidya Kondadasula, Lakhvir S Atwal, Neela Bhave, Eric Luedke, Alena Cristina Jaime-Ramirez, Amanda R Campbell, Xiaokui Mo, John C Byrd, William E Carson Iii
Natural killer (NK) cells are innate immune effector cells that play a crucial role in immune surveillance and the destruction of cancer cells. NK cells express a low-affinity receptor for the Fc or constant region of immunoglobulin G (FcγRIIIa) and multiple cytokine receptors that respond to antibody-coated targets and cytokines in the tumor microenvironment. In the present work, microarray gene expression analysis revealed that the IL-21 receptor (IL-21R) was strongly upregulated following FcR stimulation...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28638737/selective-activation-of-anti-cd73-mechanisms-in-control-of-primary-tumors-and-metastases
#18
Dipti Vijayan, Deborah S Barkauskas, Kimberley Stannard, Erin Sult, Rebecca Buonpane, Kazuyoshi Takeda, Michele W L Teng, Kris Sachsenmeier, Carl Hay, Mark J Smyth
The emerging role for CD73 in driving cancer growth and metastasis has presented opportunities to develop anti-CD73 monoclonal antibodies (mAbs) in the treatment of human cancers. Blockade of CD73 by antagonistic CD73 mAbs ameliorates tumor growth and metastasis via the inhibition of enzymatic and non-enzymatic CD73 pathways. In this study, we investigated whether Fc-receptor cross-linking represented a non-redundant mechanism by which anti-CD73 mAbs exert potent suppression of solid tumors and metastases. We engineered four anti-CD73 mAbs, each different in their ability to modulate CD73 enzymatic function and bind Fc receptors...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28638385/intercellular-communication-of-tumor-cells-and-immune-cells-after-exposure-to-different-ionizing-radiation-qualities
#19
REVIEW
Sebastian Diegeler, Christine E Hellweg
Ionizing radiation can affect the immune system in many ways. Depending on the situation, the whole body or parts of the body can be acutely or chronically exposed to different radiation qualities. In tumor radiotherapy, a fractionated exposure of the tumor (and surrounding tissues) is applied to kill the tumor cells. Currently, mostly photons, and also electrons, neutrons, protons, and heavier particles such as carbon ions, are used in radiotherapy. Tumor elimination can be supported by an effective immune response...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28638379/graft-versus-leukemia-effect-following-hematopoietic-stem-cell-transplantation-for-leukemia
#20
REVIEW
Anne M Dickinson, Jean Norden, Shuang Li, Ilona Hromadnikova, Christoph Schmid, Helga Schmetzer, Hans Jochem-Kolb
The success of hematopoietic stem cell transplantation (HSCT) lies with the ability of the engrafting immune system to remove residual leukemia cells via a graft-versus-leukemia effect (GvL), caused either spontaneously post-HSCT or via donor lymphocyte infusion. GvL effects can also be initiated by allogenic mismatched natural killer cells, antigen-specific T cells, and activated dendritic cells of leukemic origin. The history and further application of this GvL effect and the main mechanisms will be discussed and reviewed in this chapter...
2017: Frontiers in Immunology
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