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https://www.readbyqxmd.com/read/29679602/solubility-enhanced-gmyl6-fused-with-a-hexa-lysine-tag-promotes-the-cytotoxicity-of-human-nk-cells
#1
Juanjuan Liu, Yuanyuan Jin, Xiaozhou Feng, Sen Zou, Guangxin Lv, Zhifei Zhang, Zhaoyong Yang
Goat myosin light chain 6 (gMYL6) is a constituent of certain extracted immunization-induced goat anti-cancer bioactive peptides (ACBPs). However, little is known about its activity onto NK cells which are the basic cellular attackers in cancer immunotherapy for patients with malignancies. Because of the complicated extraction process and low yield of gMYL6 out of the goat ACBPs' mixture, the Nano-flow liquid chromatography and C-terminal polycationic tag expression strategy were used to identify and enrich the peptide to investigate its bioactivity against cancers/tumors...
April 18, 2018: Immunology Letters
https://www.readbyqxmd.com/read/29679556/a-novel-smac-mimetic-apg-1387-exhibited-dual-antitumor-effect-on-hbv-positive-hepatocellular-carcinoma-with-high-expression-of-ciap2-by-inducing-apoptosis-and-enhancing-innate-anti-tumor-immunity
#2
Wentao Pan, Qiuyun Luo, Xianglei Yan, Luping Yuan, Hanjie Yi, Lin Zhang, Baoxia Li, Yuxin Zhang, Jian Sun, Miao-Zhen Qiu, Da-Jun Yang
Check point inhibitor anti-PD1 antibody produced some efficacy in Hepatocellular Carcinoma (HCC) patients previously treated with sorafenib. Unfortunately, HCC patients with hepatitis B virus (HBV) infection did not respond as well as uninfected patients. Previously, SMAC mimetics-the antagonist for inhibitor of apoptosis proteins (IAPs) can rapidly reduce serum hepatitis B virus DNA in animal model. APG-1387 is a novel SMAC-mimetic, small molecule inhibitor targeting inhibitor of apoptosis proteins (IAPs)...
April 18, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29678874/mitochondrial-morphological-and-functional-reprogramming-following-cd137-4-1bb-co-stimulation
#3
Alvaro Teijeira, Sara Labiano, Saray Garasa, Inaki Etxeberria, Eva Santamaria, Ana Rouzaut, Michel Enamorado, Arantza Azpilikueta, Susana Inoges, Elixabet Bolanos-Mateo, Maria Angela Aznar, Alfonso R Sanchez-Paulete, David Sancho, Ignacio Melero
T and NK lymphocytes express CD137 (4-1BB), a costimulatory receptor of the TNFR family whose function is exploitable for cancer immunotherapy. Mitochondria regulate the function and survival of T lymphocytes. Herein, we show that CD137 costimulation provided by agonist mAb and CD137L (4-1BBL) induced mitochondria enlargement that resulted in enhanced mitochondrial mass and transmembrane potential in human and mouse CD8+ T cells. Such mitochondrial changes increased T-cell respiratory capacities and were critically dependent on mitochondrial fusion protein OPA-1 expression...
April 20, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29676151/activation-of-human-natural-killer-cells-by-graphene-oxide-templated-antibody-nanoclusters
#4
Christian Loftus, Mezida Saeed, Daniel M Davis, Iain E Dunlop
An emerging new paradigm is that immune cell activation is controlled by transient interactions between supramolecular assemblies of receptors and ligands. Current immunotherapy biologic pharmaceuticals that activate or desensitize NK cells are, however, individual molecules that do not replicate this nanoscale organization of proteins. Here, we use nanoscale graphene oxide (NGO) as a template to generate soluble nanoscale clusters of Natural Killer cell-activating antibodies. We control nanocluster size and molecular number to mimic reported values for cell surface proteins...
April 20, 2018: Nano Letters
https://www.readbyqxmd.com/read/29675689/natural-killer-cells-in-liver-diseases
#5
REVIEW
Meijuan Zheng, Haoyu Sun, Zhigang Tian
The liver has been characterized as a frontline lymphoid organ with complex immunological features such as liver immunity and liver tolerance. Liver tolerance plays an important role in liver diseases including acute inflammation, chronic infection, autoimmune disease, and tumors. The liver contains a large proportion of natural killer (NK) cells, which exhibit heterogeneity in phenotypic and functional characteristics. NK cell activation, well known for its role in the immune surveillance against tumor and pathogen-infected cells, depends on the balance between numerous activating and inhibitory signals...
April 19, 2018: Frontiers of Medicine
https://www.readbyqxmd.com/read/29674648/human-intraepithelial-lymphocytes
#6
REVIEW
Toufic Mayassi, Bana Jabri
The location of intraepithelial lymphocytes (IEL) between epithelial cells, their effector memory, cytolytic and inflammatory phenotype positions them to kill infected epithelial cells and protect the intestine against pathogens. Human TCRαβ+ CD8αβ+ IEL have the dual capacity to recognize modified self via natural killer (NK) receptors (autoreactivity) as well as foreign antigen via the T cell receptor (TCR), which is accomplished in mouse by two cell subsets, the naturally occurring TCRαβ+ CD8αα+ and adaptively induced TCRαβ+ CD8αβ+ IEL subsets, respectively...
April 20, 2018: Mucosal Immunology
https://www.readbyqxmd.com/read/29674449/induction-of-antitumor-cytotoxic-lymphocytes-using-engineered-human-primary-blood-dendritic-cells
#7
Long Wu, Huan Zhang, Yixing Jiang, Robert C Gallo, Hua Cheng
Dendritic cell (DC)-based cancer immunotherapy has achieved modest clinical benefits, but several technical hurdles in DC preparation, activation, and cancer/testis antigen (CTA) delivery limit its broad applications. Here, we report the development of immortalized and constitutively activated human primary blood dendritic cell lines (ihv-DCs). The ihv-DCs are a subset of CD11c+ /CD205+ DCs that constitutively display costimulatory molecules. The ihv-DCs can be genetically modified to express human telomerase reverse transcriptase (hTERT) or the testis antigen MAGEA3 in generating CTA-specific cytotoxic T lymphocytes (CTLs)...
April 19, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29670256/deviations-of-the-immune-cell-landscape-between-healthy-liver-and-hepatocellular-carcinoma
#8
Nataliya Rohr-Udilova, Florian Klinglmüller, Rolf Schulte-Hermann, Judith Stift, Merima Herac, Martina Salzmann, Francesca Finotello, Gerald Timelthaler, Georg Oberhuber, Matthias Pinter, Thomas Reiberger, Erika Jensen-Jarolim, Robert Eferl, Michael Trauner
Tumor-infiltrating immune cells are highly relevant for prognosis and identification of immunotherapy targets in hepatocellular carcinoma (HCC). The recently developed CIBERSORT method allows immune cell profiling by deconvolution of gene expression microarray data. By applying CIBERSORT, we assessed the relative proportions of immune cells in 41 healthy human livers, 305 HCC samples and 82 HCC adjacent tissues. The obtained immune cell profiles provided enumeration and activation status of 22 immune cell subtypes...
April 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29669207/ros-inducing-micelles-sensitize-tumor-associated-macrophages-to-tlr3-stimulation-for-potent-immunotherapy
#9
Lanlan Liu, Huamei He, Ruijing Liang, Huqiang Yi, Xiaoqing Meng, Zhikuan Chen, Hong Pan, Yifan Ma, Lintao Cai
One approach to cancer immunotherapy is the repolarization of immunosuppressive tumor-associated macrophages (TAMs) to anti-tumor M1 macrophages. The present study developed galactose-functionalized zinc protoporphyrin IX (ZnPP) grafted poly(L-lysine)-b-poly(ethyleneglycol) polypeptide micelles (ZnPP PM ) for TAM-targeted immunopotentiator delivery, which aimed at in vivo repolarization of TAMs to anti-tumor M1 macrophages. The outcomes revealed that ROS-inducing ZnPP PM demonstrated specificity for the in vitro and in vivo targeting of macrophages, elevated the level of ROS, and lowered STAT3 expression in BM-TAMs...
April 18, 2018: Biomacromolecules
https://www.readbyqxmd.com/read/29668291/reducing-the-cytotoxicity-of-lipid-nanoparticles-associated-with-a-fusogenic-cationic-lipid-in-a-natural-killer-cell-line-by-introducing-a-polycation-based-sirna-core
#10
Takashi Nakamura, Koharu Yamada, Yuki Fujiwara, Yusuke Sato, Hideyoshi Harashima
Introducing siRNA into human immune cells by an artificial delivery system continues to be a challenging issue. We previously developed a multifunctional envelope-type nanodevice (MEND) containing YSK12-C4, a fusogenic-cationic lipid, (YSK12-MEND) and succeeded in the efficient delivery of siRNA into human immune cell lines. Significant cytotoxicity, however, was observed at siRNA doses needed for gene silencing in NK-92 cells. NK-92 cells, a unique natural killer (NK) cell line, would be applicable for use in clinical NK therapy...
April 18, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29668066/mait-cell-mediated-cytotoxicity-roles-in-host-defense-and-therapeutic-potentials-in-infectious-diseases-and-cancer
#11
REVIEW
Patrick T Rudak, Joshua Choi, S M Mansour Haeryfar
Mucosa-associated invariant T (MAIT) cells are unconventional, innate-like T lymphocytes that sense the presence of MHC-related protein 1 (MR1)-restricted ligands and select inflammatory cues. Consequently, they release potent immunomodulatory mediators, including IFN-γ, TNF-α, and/or IL-17. MAIT cells can also be viewed as killer cells. They display several NK cell-associated receptors, carry granules containing cytotoxic effector molecules, and swiftly upregulate perforin and granzymes upon activation. Accordingly, MAIT cells are capable of lysing MR1-expressing cells infected with a variety of pathogenic bacteria in in vitro settings and may also mount cytotoxic responses during microbial infections in vivo...
April 18, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29666399/genotype-b-of-killer-cell-immunoglobulin-like-receptor-is-related-with-gastric-cancer-lesions
#12
Eric G Hernandez, Oswaldo Partida-Rodriguez, Margarita Camorlinga-Ponce, Miriam Nieves-Ramirez, Irma Ramos-Vega, Javier Torres, Martha Perez-Rodriguez
NK cells are important in innate immunity for their capacity to kill infected or cancer cells. The killer cell immunoglobulin-like receptors (KIR) are a family of polymorphic genes with inhibitory and activating functions. The main driving force for gastric cancer (GC) development is a chronic response, which causes an increase of NK cells in the gastric mucosa. The aim of this work was to study polymorphisms in KIR genes in patients with either GC or non-atrophic gastritis (NAG). We studied 242 patients (130 with NAG and 112 with GC) and contrasted with 146 asymptomatic individuals...
April 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29666117/novel-insights-into-the-pathogenesis-of-t-cell-lymphomas
#13
John S Van Arnam, Megan S Lim, Kojo S J Elenitoba-Johnson
T-cell lymphomas are a heterogeneous group of rare malignancies with overlapping clinical, immunologic and histologic features. Recent advances in our understanding of T-cell differentiation based on gene expression profiling, next-generation sequencing (NGS) and transgenic mouse modeling studies have better elucidated the pathogenetic mechanisms underlying the diverse biology of T-cell lymphomas. These studies show that while genetic alterations in epigenetic modifiers are implicated in all subtypes of T-cell lymphomas, specific subtypes demonstrate enrichment for particular recurrent alterations targeting specific genes...
April 17, 2018: Blood
https://www.readbyqxmd.com/read/29665931/-establishment-of-a-serum-free-culture-system-based-on-heparin-and-anti-cd16-antibody-for-expansion-of-human-cord-blood-nk-cells
#14
Qiao-Chu Wang, Liang Zhen
OBJECTIVE: To establish a novel method for ex vivo expansion of natural killer cells from human umbilical blood, so as to provide the basis for NK cell therapy. METHODS: Mononucleated cells from human umbilical blood were harvested and suspended in a serum-free medium containing 5% autologous plasma, recombinant human IL-15 (50 ng/ml) and hydrocortisone sodium succinate (5×10-8 mol/L) at a concentration of 1.5×106 /ml, then the cells were seeded into flasks pre-coated with heparin sodium (100 U/cm2 ) or/and anti-human CD16 antibody (1 µg/cm2 )...
April 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29664572/ilc2-memory-recollection-of-previous-activation
#15
REVIEW
Itziar Martinez-Gonzalez, Maryam Ghaedi, Catherine A Steer, Laura Mathä, Eric Vivier, Fumio Takei
Immunological memory, traditionally thought to belong to T and B cells, has now been extended to innate lymphocytes, including NK cells and ILC2s, myeloid cells such as macrophages, also termed "trained immunity" and more recently to epithelial stem cells. In this review, we discuss the mechanisms underlying memory generation on ILC2s and speculate about their potential role in human allergic diseases, such as asthma. Moreover, we examine the relevance of the spontaneous ILC2 activation in the lung during the neonatal period in order to efficiently respond to stimuli later in life...
May 2018: Immunological Reviews
https://www.readbyqxmd.com/read/29663988/-unfractionated-heparin-inhibits-the-activation-of-endothelial-cells-by-decreasing-the-degree-of-hoxa9-reduced-expression
#16
Rui Yang, Xiaojuan Zhang, Yingjian Liang, Xiaochun Ma
OBJECTIVE: To study unfractionated heparin (UFH) effect on the expression of HOXA9 in activation of human umbilical vein endothelial cells (HUVECs) induced by lipopolysaccharide (LPS). METHODS: HUVECs were cultured and they were randomly divided into four groups (n = 5) for the challenge respectively: (1) control group (with an equal volume of phosphate buffer saline); (2) LPS group (LPS 10 mg/L); (3) UFH group (UFH 10 kU/L); (4) UFH+LPS group (10 kU/L UFH 30 minutes + LPS 10 mg/L)...
April 2018: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
https://www.readbyqxmd.com/read/29662662/health-effects-of-a-forest-environment-on-natural-killer-cells-in-humans-an-observational-pilot-study
#17
Tsung-Ming Tsao, Ming-Jer Tsai, Jing-Shiang Hwang, Wen-Fang Cheng, Chang-Fu Wu, Charles-C K Chou, Ta-Chen Su
Health effect assessments based on natural killer (NK) cells are an important emerging area of human health. We recruited 90 forest staff members in Xitou, Taiwan and 110 urban staff members in Taipei to investigate the health effects of forest environment exposure on NK cells (CD3- /CD56+ ) and activating NK cells (CD3- /CD56+ /CD69+ ) in humans. We also invited 11 middle-aged volunteers in a pilot study to participate in a five-day/four-night forest trip to Xitou forest to investigate the health effects of a forest trip on NK cells and activating NK cells...
March 27, 2018: Oncotarget
https://www.readbyqxmd.com/read/29662493/age-related-changes-in-the-natural-killer-cell-response-to-seasonal-influenza-vaccination-are-not-influenced-by-a-synbiotic-a-randomised-controlled-trial
#18
Agnieszka Przemska-Kosicka, Caroline E Childs, Catherine Maidens, Honglin Dong, Susan Todd, Margot A Gosney, Kieran Michael Tuohy, Parveen Yaqoob
Natural killer (NK) cells are an important component of the immune response to influenza infection, but are subject to alteration during aging, which may play a role in impaired response to infection and vaccination in older people. Enhancement of NK cell activity could, therefore, present a means to improve the immune response to vaccination in older subjects, and pre- and probiotics offer an opportunity to modulate antiviral defenses via alteration of the gut microbiota. This study investigated the effect of a novel probiotic, Bifidobacterium longum bv...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29662484/nkg2d-and-its-ligands-one-for-all-all-for-one
#19
REVIEW
Alessandra Zingoni, Rosa Molfetta, Cinzia Fionda, Alessandra Soriani, Rossella Paolini, Marco Cippitelli, Cristina Cerboni, Angela Santoni
The activating receptor NKG2D is peculiar in its capability to bind to numerous and highly diversified MHC class I-like self-molecules. These ligands are poorly expressed on normal cells but can be induced on damaged, transformed or infected cells, with the final NKG2D ligand expression resulting from multiple levels of regulation. Although redundant molecular mechanisms can converge in the regulation of all NKG2D ligands, different stimuli can induce specific cellular responses, leading to the expression of one or few ligands...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29661825/nkp46-calibrates-tumoricidal-potential-of-type-1-innate-lymphocytes-by-regulating-trail-expression
#20
Gleb Turchinovich, Stefan Ganter, Anne Bärenwaldt, Daniela Finke
NK cells are a subset of group 1 innate lymphocytes that recognize and eliminate virus-infected and transformed cells. During the course of their development, NK cells acquire a repertoire of activating and inhibitory receptors, which ultimately define their reactivity against target cells. The array of receptors and their specificity during early developmental stages will control and imprint functional properties of NK cells, a process known as "NK cell education." Innate lymphoid cells (ILCs) are a diverse group of lymphocytes, which, like NK cells, do not rely on somatically rearranged Ag receptors for recognition...
April 16, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
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