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https://www.readbyqxmd.com/read/29050360/immunomodulatory-and-antitumor-effects-of-type-i-interferons-and-their-application-in-cancer-therapy
#1
REVIEW
Ruan F V Medrano, Aline Hunger, Samir Andrade Mendonça, José Alexandre M Barbuto, Bryan E Strauss
During the last decades, the pleiotropic antitumor functions exerted by type I interferons (IFNs) have become universally acknowledged, especially their role in mediating interactions between the tumor and the immune system. Indeed, type I IFNs are now appreciated as a critical component of dendritic cell (DC) driven T cell responses to cancer. Here we focus on IFN-α and IFN-β, and their antitumor effects, impact on immune responses and their use as therapeutic agents. IFN-α/β share many properties, including activation of the JAK-STAT signaling pathway and induction of a variety of cellular phenotypes...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050291/natural-killer-cell-activity-for-ifn-gamma-production-as-a-supportive-diagnostic-marker-for-gastric-cancer
#2
Jongmi Lee, Ki Hyun Park, Ji Hyeong Ryu, Hyun Jin Bae, Aeran Choi, Hyeyoung Lee, Jihyang Lim, Kyungja Han, Cho Hyun Park, Eun Sun Jung, Eun-Jee Oh
BACKGROUND/AIM: Decreased Natural killer cell activity (NKA) for interferon-gamma production (NKA-IFNγ) has been reported in cancer patients. The aim of this study was to determine the diagnostic performance of NKA-IFNγ for gastric cancer (GC). RESULTS: NKA-IFNγ levels were decreased in 261 GC patients with all stages of tumor compared to those in 48 healthy donors (P < 0.001), and lower levels of NKA-IFNγ were associated with higher GC stages. NKA-IFNγ levels were also associated with clinicopathological parameters including tumor size, depth of invasion, and lymph node metastasis...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050212/recombination-activating-gene-2-null-severe-combined-immunodeficient-pigs-and-mice-engraft-human-induced-pluripotent-stem-cells-differently
#3
Yun-Jung Choi, EunSu Kim, Abu Musa Md Talimur Reza, Kwonho Hong, Hyuk Song, Chankyu Park, Seong-Keun Cho, Kiho Lee, Randall S Prather, Jin-Hoi Kim
This study comparatively investigated the transcriptional, physiological, and phenotypic differences of the immune disorder between severe combined immunodeficient (SCID) mouse and pig models. We discovered that the recombination activating gene-2 (Rag-2) SCID mice, but not RAG-2 SCID pigs, showed intense, infrequent, and mild cluster of CD3(+)-, CD4(+)-, and CD8(+) signals respectively, suggesting that distinct species-specific effects exist. Furthermore, the expression of six relevant genes (NFATC1, CD79B, CD2, BLNK, FOXO1, and CD40) was more downregulated than that in the Rag-2 SCID mice, which provides a partial rationale for the death of T/B cells in the lymphoid organs of RAG-2 SCID pigs but not in Rag-2 SCID mice...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29047161/donor-lymphocyte-infusion-and-methotrexate-for-immune-recovery-after-t-cell-depleted-haploidentical-transplantation
#4
Andrew L Gilman, Wing Leung, Morton J Cowan, Mark Cannon, Stacy Epstein, Carrie Barnhart, Krishna Shah, Michelle Hyland, Tracy Fukes, Anastasia Ivanova
CD34+ cell selection minimizes graft-versus-host disease (GVHD) after haploidentical donor stem cell transplant but is associated with slow immune recovery and infections. We report a Phase I/II study of prophylactic donor lymphocyte infusion (DLI) followed by methotrexate (MTX) GVHD prophylaxis after CD34-selected haploidentical donor transplant. A prophylactic DLI was given between day +30 and +42. Rituximab was given with DLI for the last 10 patients. The goal of the study was to determine a DLI dose that would result in a CD4+ cell count > 100/µL at Day +120 in ≥ 66% of patients with ≤ 33% grade II-III, ≤ 17% grade III, and no grade IV acute GVHD by Day +180...
October 19, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/29046274/genetic-depletion-or-hyperresponsiveness-of-natural-killer-cells-do-not-affect-atherosclerosis-development
#5
Wared Nour Eldine, Jeremie Joffre, Kazem Zibara, Andreas Giraud, Bruno Esposito, Lynda Zeboudj, José Vilar, Megumi Terada, Patrick Bruneval, Eric Vivier, Hafid Ait-Oufella, Ziad Mallat, Sophie Ugolini, Alain Tedgui
Rationale: Chronic inflammation is central in the development of atherosclerosis. Both innate and adaptive immunity are involved. Although several studies have evaluated the functions of NK cells in experimental animal models of atherosclerosis, it is not yet clear whether NK cells behave as protective or pro-atherogenic effectors. One of the main caveats of previous studies was the lack of specificity in targeting loss- or gain-of-function of NK cells. Objective: We used two selective genetic approaches to investigate the role of NK cells in atherosclerosis: 1) Ncr1i(Cre/+)R26(lsl-DTA/+) mice in which NK cells were depleted, 2) Noé mice in which NK cells are hyperresponsive...
October 18, 2017: Circulation Research
https://www.readbyqxmd.com/read/29045900/molecular-and-functional-characterization-of-lymphoid-progenitor-subsets-reveals-a-bipartite-architecture-of-human-lymphopoiesis
#6
Kutaiba Alhaj Hussen, Thien-Phong Vu Manh, Fabien Guimiot, Elisabeth Nelson, Emna Chabaane, Marc Delord, Maxime Barbier, Claire Berthault, Nicolas Dulphy, Antonio José Alberdi, Odile Burlen-Defranoux, Gerard Socié, Jean Christophe Bories, Jerôme Larghero, Valérie Vanneaux, Els Verhoeyen, Thierry Wirth, Marc Dalod, Jean Claude Gluckman, Ana Cumano, Bruno Canque
The classical model of hematopoiesis established in the mouse postulates that lymphoid cells originate from a founder population of common lymphoid progenitors. Here, using a modeling approach in humanized mice, we showed that human lymphoid development stemmed from distinct populations of CD127(-) and CD127(+) early lymphoid progenitors (ELPs). Combining molecular analyses with in vitro and in vivo functional assays, we demonstrated that CD127(-) and CD127(+) ELPs emerged independently from lympho-mono-dendritic progenitors, responded differently to Notch1 signals, underwent divergent modes of lineage restriction, and displayed both common and specific differentiation potentials...
October 17, 2017: Immunity
https://www.readbyqxmd.com/read/29045618/cd27-co-stimulation-increases-the-abundance-of-regulatory-t-cells-and-reduces-atherosclerosis-in-hyperlipidaemic-mice
#7
Holger Winkels, Svenja Meiler, Dirk Lievens, David Engel, Charlotte Spitz, Christina Bürger, Linda Beckers, Angelika Dandl, Sigrid Reim, Maiwand Ahmadsei, Helene Hartwig, Lesca M Holdt, Michael Hristov, Remco T A Megens, Martin M Schmitt, Eric A Biessen, Jannie Borst, Alexander Faussner, Christian Weber, Esther Lutgens, Norbert Gerdes
Aims: The co-stimulatory receptor CD27 modulates responses of T cells, B cells, and NK cells. Various T cell subsets participate in atherogenesis. However, the role of CD27 in atherosclerosis remains unexplored. Methods and results: Here we investigated the effect of bone marrow-derived and systemic CD27 deficiency in Apolipoprotein E-deficient (Apoe-/-) mice in early and advanced stages of atherosclerosis. Lethally-irradiated Apoe-/- mice reconstituted with Cd27-/-Apoe-/- bone marrow and consuming an atherogenic diet displayed a markedly increased plaque size and lesional inflammation compared to mice receiving Cd27+/+Apoe-/- bone marrow...
October 16, 2017: European Heart Journal
https://www.readbyqxmd.com/read/29045069/association-of-natural-killer-cell-ligand-polymorphism-hla-c-asn80lys-with-the-development-of-anti-ssa-ro-associated-congenital-heart-block
#8
Hannah C Ainsworth, Miranda C Marion, Tiziana Bertero, Antonio Brucato, Rolando Cimaz, Nathalie Costedoat-Chalumeau, Micaela Fredi, Patrick Gaffney, Jennifer Kelly, Kateri Levesque, Alice Maltret, Nathalie Morel, Veronique Ramoni, Amelia Ruffatti, Carl D Langefeld, Jill P Buyon, Robert M Clancy
OBJECTIVE: Fetal exposure to maternal anti-SSA/Ro antibodies is necessary but not sufficient for the development of autoimmune congenital heart block (CHB), suggesting that other factors, such as fetal genetic predisposition, are important. Given the previously described association between major histocompatibility complex alleles and CHB risk, we undertook the present study to test the hypothesis that a variant form of HLA-C Asn80Lys, which binds with high affinity to an inhibitory killer cell immunoglobulin-like receptor (KIR) and thus renders natural killer (NK) cells incapable of restricting inflammation, contributes to the development of CHB...
October 17, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29043703/the-effects-of-dienogest-on-macrophage-and-natural-killer-cells-in-adenomyosis-a-randomized-controlled-study
#9
Saowapak Prathoomthong, Yada Tingthanatikul, Srithean Lertvikool, Nittaya Rodratn, Wanwisa Waiyaput, Kanthanadon Dittharot, Morakot Sroyraya, Areepan Sophonsritsuk
Background: Progestin has been used for symptomatic treatment of adenomyosis, although its effect on the immune system has not been studied. The aim of this study was to investigate the changes of macrophage and natural killer (NK) cell infiltration in tissues obtained from women with adenomyosis who did or did not receive oral progestin dienogest. MATERIALS AND METHODS: In this randomized controlled clinical trial study, 24 patients with adenomyosis who required hysterectomy were enrolled...
January 2018: International Journal of Fertility & Sterility
https://www.readbyqxmd.com/read/29043241/an-unusual-case-of-metachronous-nk-t-cell-lymphoma-and-interdigitating-dendritic-cell-sarcoma
#10
So Yeon Hwang, In Sook Woo, Yosep Chong, Chang Suk Kang, Chi Wha Han, Yun Hwa Jung
No abstract text is available yet for this article.
September 2017: Blood Research
https://www.readbyqxmd.com/read/29042994/immunological-mechanism-of-low-dose-priming-radiation-resistance-in-walker-256-tumor-model-mice
#11
Li Feng, Ling Qin, Dan Guo, Daping Deng, Feng Lu, Hailiang Li, Narisu Bao, Xiting Yang, Hongyu Ding, Jianguo Li
The aim of the present study was to investigate whether low-dose priming radiation induces antitumor immunity that can be augmented by the modulation of natural killer (NK) cell and cytokine activity using a mouse tumor model. Walker-256 cells were injected into the right flank of male BALB/c mice. At 7 days after inoculation, mice were divided into three groups, including group 1,2,3. In group 1 the mice were without radiation, in group 2 the mice were received 2 Gy radiation only, and in group 3 the mice were radiated with a priming dose of 75 mGy followed by 2 Gy radiation after 24 h...
October 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29042780/frequencies-of-circulating-b-and-t-lymphocytes-as-indicators-for-stroke-outcomes
#12
Yanling Wang, Jihong Liu, Xuemei Wang, Zongjian Liu, Fengwu Li, Fenghua Chen, Xiaokun Geng, Zhili Ji, Huishan Du, Xiaoming Hu
BACKGROUND: Stroke has high mortality and morbidity. Biomarkers are required for to predict stroke outcomes, which could help clinicians to provide rationale approaches for patient management. The dynamic changes in circulating immune cells have been reported in stroke patients and animal models of stroke. AIM: The aim of this study was to explore biomarkers to predict stroke outcomes by investigating the relationship between the frequencies of circulating immune cells and stroke outcomes...
2017: Neuropsychiatric Disease and Treatment
https://www.readbyqxmd.com/read/29042488/natural-killer-cells-mediate-pathophysiology-in-response-to-reduced-uterine-perfusion-pressure
#13
Jamil Elfarra, Lorena M Amaral, Maggie McCalmon, Jeremy D Scott, Mark W Cunningham, Ashley Gnam, Tarek Ibrahim, Babbette LaMarca, Denise C Cornelius
Preeclampsia is associated with hypertension, small-for-gestational-age babies and increased cytolytic natural killer (NK) cells. The specific role of cytolytic NK cells in the pathophysiology of preeclampsia has not been clearly defined. We hypothesized that Reduced Uterine Perfusion Pressure (RUPP) stimulates proliferation and cytolytic activation of NK cells, and that reducing NK cells in RUPP would prevent hypertension, intrauterine growth restriction, and inflammation in response to placental ischemia...
October 17, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29042417/restoration-of-natural-killer-cell-anti-metastatic-activity-by-il-12-and-checkpoint-blockade
#14
Isabel Ohs, Laura Ducimetiere, Joana Marinho, Paulina Kulig, Burkhard Becher, Sonia Tugues
Immune checkpoint therapies target tumor antigen-specific T cells, but less is known about their effects on natural killer (NK) cells, which help control metastasis. In studying the development of lung metastases, we found that NK cells lose their cytotoxic capacity and acquire a molecular signature defined by the expression of co-inhibitory receptors. In an effort to overcome this suppressive mechanism, we evaluated NK cell responses to the immunostimulatory cytokine IL-12. Exposure to IL-12 rescued the cytotoxicity of NK cells but also led to the emergence of an immature NK cell population which expressed high levels of the co-inhibitory molecules PD-1, Lag-3 and TIGIT, thereby limiting NK cell-mediated control of pulmonary metastases...
October 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/29040918/tumor-cryoablation-in-combination-with-natural-killer-cells-therapy-and-herceptin-in-patients-with-her2-overexpressing-recurrent-breast-cancer
#15
Shuzhen Liang, Lizhi Niu, Kecheng Xu, Xiaohua Wang, Yingqing Liang, Mingjie Zhang, Jibing Chen, Mao Lin
In this study, we investigated the clinical benefits of a combination of tumor cryoablation with natural killer (NK) cells therapy and Herceptin for human epidermal growth factor (HER) 2-overexpressing recurrent breast cancer. From May 2015 to May 2016, 48 patients who met the enrollment criteria were assigned to three groups (n=16): cryoablation group (group I), cryoablation-NK cells therapy group (group II) and cryoablation-NK cells therapy-Herceptin group (group III). Safety and short-term effects were evaluated...
October 13, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29040754/development-of-unique-cytotoxic-chimeric-antigen-receptors-based-on-human-scfv-targeting-b7h6
#16
Casey K Hua, Albert T Gacerez, Charles L Sentman, Margaret E Ackerman
As a stress-inducible natural killer (NK) cell ligand, B7H6 plays a role in innate tumor immunosurveillance and is a fairly tumor selective marker expressed on a variety of solid and hematologic cancer cells. Here, we describe the isolation and characterization of a new family of single chain fragment variable (scFv) molecules targeting the human B7H6 ligand. Through directed evolution of a yeast surface displayed non-immune human-derived scFv library, eight candidates comprising a single family of clones differing by up to four amino acid mutations and exhibiting nM avidities for soluble B7H6-Ig were isolated...
October 11, 2017: Protein Engineering, Design & Selection: PEDS
https://www.readbyqxmd.com/read/29040326/mycobacterium-tuberculosis-infection-modulates-adipose-tissue-biology
#17
Macarena Beigier-Bompadre, Georgina N Montagna, Anja A Kühl, Laura Lozza, January Weiner, Andreas Kupz, Alexis Vogelzang, Hans-Joachim Mollenkopf, Delia Löwe, Silke Bandermann, Anca Dorhoi, Volker Brinkmann, Kai Matuschewski, Stefan H E Kaufmann
Mycobacterium tuberculosis (Mtb) primarily resides in the lung but can also persist in extrapulmonary sites. Macrophages are considered the prime cellular habitat in all tissues. Here we demonstrate that Mtb resides inside adipocytes of fat tissue where it expresses stress-related genes. Moreover, perigonadal fat of Mtb-infected mice disseminated the infection when transferred to uninfected animals. Adipose tissue harbors leukocytes in addition to adipocytes and other cell types and we observed that Mtb infection induces changes in adipose tissue biology depending on stage of infection...
October 17, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29040297/decreased-nk-cell-immunity-in-kidney-transplant-recipients-late-post-transplant-and-increased-nk-cell-immunity-in-patients-with-recurrent-miscarriage
#18
Li Zhu, Mostafa Aly, Haihao Wang, Hristos Karakizlis, Rolf Weimer, Christian Morath, Ruben Jeremias Kuon, Bettina Toth, Gerhard Opelz, Volker Daniel
BACKGROUND: There is evidence that NK-cell reactivity might affect graft outcome in transplant recipients and pregnancy in women. METHOD: NK-cell subsets were determined in whole blood using eight-colour-fluorescence flow cytometry in patients before and after renal transplantation, patients with recurrent miscarriage (RM) and healthy controls (HC). RESULTS: Patients late post-transplant (late-Tx) with functioning renal transplants showed abnormally low CD56dimCD16+ NK-cells containing both perforin and granzyme (vs HC p = 0...
2017: PloS One
https://www.readbyqxmd.com/read/29038795/immune-engineering-from-systems-immunology-to-engineering-immunity
#19
Ning Jiang
The smallpox vaccine represents the earliest attempt in engineering immunity. The recent success of chimeric antigen receptor T cells (CAR-T cells) in cancer once again demonstrates the clinical potential of immune engineering. Inspired by this success, diverse approaches have been used to boost various aspects of immunity: engineering dendritic cells (DCs), natural killer (NK) cells, T cells, antibodies, cytokines, small peptides, and others. With recent development of various high-throughput technologies (of which engineers, especially biomedical engineers/bioengineers contributed significantly), such as immune repertoire sequencing, and analytical methods, a systems level of understanding immunity (or the lack of it) beyond model animals has provided critical insights into the human immune system...
March 2017: Curr Opin Biomed Eng
https://www.readbyqxmd.com/read/29038620/dengue-virus-induces-nk-cell-activation-through-trail-expression-during-infection
#20
Mariana Gandini, Fabienne Petitinga-Paiva, Cíntia Ferreira Marinho, Gladys Correa, Luzia Maria De Oliveira-Pinto, Luiz José de Souza, Rivaldo Venâncio Cunha, Claire Fernandes Kubelka, Elzinandes Leal de Azeredo
Dengue is an acute febrile illness with a wide spectrum of signs and symptoms ranging from mild to severe forms characterized by plasma leakage that can be fatal. NK cells are one of the main effectors in early infection and may play an important role in dengue pathogenesis. We investigated NK cell involvement during dengue infection. A higher frequency of NK cell subsets and TRAIL+NK cells was found in mild DF cases when compared to that in severe cases or healthy donors. NK activation markers such as CD107a and TLR3 were upregulated in patients' cells compared to those in healthy donors...
2017: Mediators of Inflammation
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