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https://www.readbyqxmd.com/read/28636546/changes-of-peripheral-lymphocyte-subsets-and-cytokine-environment-during-ageing-and-deteriorating-gastrointestinal-tract-health-status
#1
Jing Wang, Guodong Yang, Dongfang Wang, Kuiliang Liu, Yongchao Ma, Hong Liu, Jing Wu, Min Fang
Human immune senescence accompanies with the physical and physiological frailty. The functional change and shift of NK, NKT and T cell subsets by ageing have been widely studied. However, it remains largely unclear how the ageing and disease conditions affect the distribution of lymphocytes. In the present study, 233 subjects with age range from 20 to 87 year old, including healthy people, people with chronic gastrointestinal tract disease or cancers were investigated. We found that the proportion of NK cells, CD8+ T cells and NKT cells remained relatively unchanged with ageing...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28629761/cytokines-for-the-induction-of-antitumor-effectors-the-paradigm-of-cytokine-induced-killer-cik-cells
#2
Elisa Cappuzzello, Roberta Sommaggio, Paola Zanovello, Antonio Rosato
Cytokine-Induced killer (CIK) cells are raising growing interest in cellular antitumor therapy, as they can be easily expanded with a straightforward and inexpensive protocol, and are safe requiring only GMP-grade cytokines to obtain very high amounts of cytotoxic cells. CIK cells do not need antigen-specific stimuli to be activated and proliferate, as they recognize and destroy tumor cells in an HLA-independent fashion through the engagement of NKG2D. In several preclinical studies and clinical trials, CIK cells showed a reduced alloreactivity compared to conventional T cells, even when challenged across HLA-barriers; only in a few patients, a mild GVHD occurred after treatment with allogeneic CIK cells...
June 3, 2017: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/28628025/-phenotype-facilities-of-lymphocytes-in-hemorrhagic-fever-with-renal-syndrome
#3
M Ivanov, I Balmasova, Z Vasnyova
Hemorrhagic fever with renal syndrome (HFRS) is a feral herd disease caused by hantaviruses. HERS may be severe and its manifestations include acute renal failure, intoxication, hemorrhages and pain syndrome. Hantaviruses as pathogen of HFRS wield considerable influence on the character of the immune response, in particular, is capable of lymphocytic cytolysis suppressing. It was found that cytotoxic T lymphocytes along with NKT and CD8 + regulatory T cells play the key role in the immune mechanisms of hemorrhagic fever with renal syndrome...
May 2017: Georgian Medical News
https://www.readbyqxmd.com/read/28622272/nk-cell-derived-exosomes-from-nk-cells-previously-exposed-to-neuroblastoma-cells-augment-the-antitumor-activity-of-cytokine-activated-nk-cells
#4
Alireza Shoae-Hassani, Amir Ali Hamidieh, Maryam Behfar, Rashin Mohseni, Seyed A Mortazavi-Tabatabaei, Shahab Asgharzadeh
Immune cell-derived exosomes can increase immunity against tumors. In contrast, tumor-derived exosomes can reduce the immunity and can change the tumor microenvironment to further develop and provide metastasis. These effects take place by an alteration in the innate and adaptive immune cell functions. In this experiment, we studied the natural killer (NK) cells' effectiveness on tumor cells after expansion and thereafter incubated it with exosomes. The exosomes were derived from 2 populations of NK cells: (1) naive NK cells and, (2) NK cells previously exposed to neuroblastoma (NB) cells...
June 15, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28617830/on-treatment-decrease-of-nkg2d-correlates-to-early-emergence-of-clinically-evident-hepatocellular-carcinoma-after-interferon-free-therapy-for-chronic-hepatitis-c
#5
Po-Sung Chu, Nobuhiro Nakamoto, Nobuhito Taniki, Keisuke Ojiro, Takeru Amiya, Yuko Makita, Hiroko Murata, Akihiro Yamaguchi, Shunsuke Shiba, Rei Miyake, Tadashi Katayama, Aya Ugamura, Akihiko Ikura, Karin Takeda, Hirotoshi Ebinuma, Hidetsugu Saito, Takanori Kanai
BACKGROUND AND AIMS: Interferon (IFN)- free direct antiviral agents (DAAs) with rapid HCV eradication might evoke immunological reconstitutions, and some early recurrences of HCC after IFN-free DAAs have been reported. This study aimed to investigate whether natural killer group 2, member D (NKG2D) predicts early emergence of HCC after IFN-free DAAs. METHODS: We conducted a clinical practice-based observational study of 101 patients infected with genotype 1 HCV who received IFN-free (DAAs), and stratified them into those who did or did not develop early (i...
2017: PloS One
https://www.readbyqxmd.com/read/28615524/interleukin-15-stimulates-natural-killer-cell-mediated-killing-of-both-human-pancreatic-cancer-and-stellate-cells
#6
Jonas R M Van Audenaerde, Jorrit De Waele, Elly Marcq, Jinthe Van Loenhout, Eva Lion, Johan M J Van den Bergh, Ralf Jesenofsky, Atsushi Masamune, Geert Roeyen, Patrick Pauwels, Filip Lardon, Marc Peeters, Evelien L J Smits
Pancreatic ductal adenocarcinoma (PDAC) is the 4th leading cause of cancer-related death in Western countries with a 5-year survival rate below 5%. One of the hallmarks of this cancer is the strong desmoplastic reaction within the tumor microenvironment (TME), orchestrated by activated pancreatic stellate cells (PSC). This results in a functional and mechanical shield which causes resistance to conventional therapies. Aiming to overcome this resistance by tackling the stromal shield, we assessed for the first time the capacity of IL-15 stimulated natural killer (NK) cells to kill PSC and pancreatic cancer cells (PCC)...
May 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28615199/impaired-downregulation-of-nkg2d-ligands-by-nef-protein-from-elite-controllers-sensitizes-hiv-1-infected-cells-to-adcc
#7
Nirmin Alsahafi, Jonathan Richard, Jérémie Prévost, Mathieu Coutu, Nathalie Brassard, Matthew S Parsons, Daniel E Kaufmann, Mark Brockman, Andrés Finzi
HIV-1 Nef clones isolated from a rare subset of HIV-1-infected elite controllers (EC), with the ability to suppress viral load to undetectable levels in the absence of antiretroviral therapy, are unable to fully downregulate CD4 from the plasma membrane of CD4+ T cells. Residual CD4 left at the plasma membrane allows Env-CD4 interaction, which leads to increased exposure of Env CD4-induced epitopes and increases susceptibility of infected cells to antibody-dependent cellular cytotoxicity (ADCC). ADCC is mediated largely by natural killer (NK) cells, which control their activation status through the cumulative signals received through activating and inhibitory receptors...
June 14, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28612942/cytomegalovirus-vector-expressing-rae-1%C3%AE-induces-enhanced-anti-tumor-capacity-of-murine-cd8-t-cells
#8
Tihana Tršan, Kristina Vuković, Petra Filipović, Ana Lesac Brizić, Niels A W Lemmermann, Kilian Schober, Dirk H Busch, William J Britt, Martin Messerle, Astrid Krmpotić, Stipan Jonjić
Designing CD8(+) T-cell vaccines, which would provide protection against tumors is still considered a great challenge in immunotherapy. Here we show the robust potential of cytomegalovirus (CMV) vector expressing the NKG2D ligand RAE-1γ as CD8(+) T cell-based vaccine against malignant tumors. Immunization with the CMV vector expressing RAE-1γ, delayed tumor growth or even provided complete protection against tumor challenge in both prophylactic and therapeutic settings. Moreover, a potent tumor control in mice vaccinated with this vector can be further enhanced by blocking the immune checkpoints TIGIT and PD-1...
June 14, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28603523/kir3ds1-mediated-recognition-of-hla-b51-modulation-of-kir3ds1-responsiveness-by-self-hla-b-allotypes-and-effect-on-nk-cell-licensing
#9
Simona Carlomagno, Michela Falco, Maria Bono, Claudia Alicata, Lucia Garbarino, Michela Mazzocco, Lorenzo Moretta, Alessandro Moretta, Simona Sivori
Several studies described an association between killer-cell immunoglobulin-like receptor (KIR)/HLA gene combinations and clinical outcomes in various diseases. In particular, an important combined role for KIR3DS1 and HLA-B Bw4-I80 in controlling viral infections and a higher protection against leukemic relapses in donor equipped with activating KIRs in haplo-HSCT has been described. Here, we show that KIR3DS1 mediates positive signals upon recognition of HLA-B*51 (Bw4-I80) surface molecules on target cells and that this activation occurs only in Bw4-I80(neg) individuals, including those carrying particular KIR/HLA combination settings...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28585428/anti-hepatocarcinoma-activity-of-tt-1-an-analog-of-melittin-combined-with-interferon-%C3%AE-via-promoting-the-interaction-of-nkg2d-and-mica
#10
Lan-Lan Wan, Da-Qi Zhang, Jin-Nan Zhang, Li-Qun Ren
Hepatocarcinoma is one of the malignant cancers with significant morbidity and mortality. Immunotherapy has emerged in clinical treatment, owing to the limitation and severe side effects of chemotherapy. In the immune system, natural killer (NK) cells are important effectors required to eliminate malignant tumor cells without the limitation of major histocompatibility complex (MHC) molecule issues. Hence, treatment which could stimulate NK cells is of great interest. Here, we investigated the efficacy of the combined therapy of TT-1 (a mutant of melittin) and interferon-α (IFN-α) on NK cells and human liver cancer HepG-2/Huh7 cells in vitro and in vivo, as well as the mechanism involved...
June 2017: Journal of Zhejiang University. Science. B
https://www.readbyqxmd.com/read/28581441/nk-cell-heparanase-controls-tumor-invasion-and-immune-surveillance
#11
Eva M Putz, Alyce J Mayfosh, Kevin Kos, Deborah S Barkauskas, Kyohei Nakamura, Liam Town, Katharine J Goodall, Dean Y Yee, Ivan Kh Poon, Nikola Baschuk, Fernando Souza-Fonseca-Guimaraes, Mark D Hulett, Mark J Smyth
NK cells are highly efficient at preventing cancer metastasis but are infrequently found in the core of primary tumors. Here, have we demonstrated that freshly isolated mouse and human NK cells express low levels of the endo-β-D-glucuronidase heparanase that increase upon NK cell activation. Heparanase deficiency did not affect development, differentiation, or tissue localization of NK cells under steady-state conditions. However, mice lacking heparanase specifically in NK cells (Hpsefl/fl NKp46-iCre mice) were highly tumor prone when challenged with the carcinogen methylcholanthrene (MCA)...
June 5, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28578917/stat3-inhibition-by-sta21-increases-cell-surface-expression-of-micb-and-the-release-of-soluble-micb-by-gastric-adenocarcinoma-cells
#12
Macarena Garrido-Tapia, Carolina J Hernández, Gabriel Ascui, Karina Kramm, Marcela Morales, Valentina Ga Rate, Roberto Zúñiga, Marco Bustamante, Juan Carlos Aguillón, Diego Catala N, Carolina H Ribeiro, Mari A Carmen Molina
NKG2D is an activating receptor expressed on NK cells that binds to a variety of ligands, including MICA and MICB. These cell surface glycoproteins are overexpressed under cellular transformation, thus playing an important role in cell-mediated immune response to tumors. STAT3 is a transcription factor that is constitutively active in cancer. It negatively regulates MICA expression on target cells, while its inhibition enhances NK cell cytotoxicity against tumors. In this work, we aimed to describe the effect of STAT3 signaling inhibition by STA21 on the regulation of MICB expression in gastric adenocarcinoma cells and its effect on the cytotoxic function of NK cells...
May 23, 2017: Immunobiology
https://www.readbyqxmd.com/read/28576980/tlr9-regulates-the-nf-%C3%AE%C2%BAb-nlrp3-il-1%C3%AE-pathway-negatively-in-salmonella-induced-nkg2d-mediated-intestinal-inflammation
#13
Yan Li, Meifang Liu, Zengyan Zuo, Jing Liu, Xin Yu, Yun Guan, Renhui Zhan, Qiuju Han, Jian Zhang, Rongbin Zhou, Rui Sun, Zhigang Tian, Cai Zhang
TLRs are key sensors for conserved bacterial molecules and play a critical role in host defense against invading pathogens. Although the roles of TLRs in defense against pathogen infection and in maintaining gut immune homeostasis have been studied, the precise functions of different TLRs in response to pathogen infection in the gut remain elusive. The present study investigated the role of TLR signaling in defense against the Gram-negative bacterial pathogen Salmonella typhimurium The results indicated that TLR9-deficient mice were more susceptible to S...
June 2, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28576831/shifting-the-balance-of-activating-and-inhibitory-natural-killer-receptor-ligands-on-braf-v600e-melanoma-lines-with-vemurafenib
#14
Alexandra Frazao, Marina Colombo, Emmanuelle Fourmentraux-Neves, Meriem Messaoudene, Sylvie Rusakiewicz, Laurence Zitvogel, Eric Vivier, Frederic Vely, Florence Faure, Brigitte Dreno, Houssem Benlalam, Fanny Bouquet, Ariel Savina, Eric Pasmant, Antoine Toubert, Marie Francoise Avril, Anne Caignard
Over 60% of human melanoma tumors bear a mutation in the BRAF gene. The most frequent mutation is a substitution at codon 600 (V600E), leading to a constitutively active BRAF and overactivation of the mitogen-activated protein kinase (MAPK) pathway. Patients harboring mutated BRAF respond to kinase inhibitors such as vemurafenib. However, these responses are transient and relapses are frequent. Melanoma cells are efficiently lysed by activated natural killer (NK) cells. Melanoma cells express several stress-induced ligands that are recognized by activating NK cell receptors...
June 2, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28574833/new-interleukin-15-superagonist-il-15sa-significantly-enhances-graft-versus-tumor-activity
#15
Cavan P Bailey, Tulin Budak-Alpdogan, Christopher T Sauter, Michelle M Panis, Cihangir Buyukgoz, Emily K Jeng, Hing C Wong, Neal Flomenberg, Onder Alpdogan
Interleukin-15 (IL-15) is a potent cytokine that increases CD8+ T and NK cell numbers and function in experimental models. However, obstacles remain in using IL-15 therapeutically, specifically its low potency and short in vivo half-life. To help overcome this, a new IL-15 superagonist complex comprised of an IL-15N72D mutation and IL-15RαSu/Fc fusion (IL-15SA, also known as ALT-803) was developed. IL-15SA exhibits a significantly longer serum half-life and increased in vivo activity against various tumors...
May 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28560327/antibody-mediated-neutralization-of-soluble-mic-significantly-enhances-ctla4-blockade-therapy
#16
Jingyu Zhang, Dai Liu, Guangfu Li, Kevin F Staveley-O'Carroll, Julie N Graff, Zihai Li, Jennifer D Wu
Antibody therapy targeting cytotoxic T lymphocyte-associated antigen 4 (CTLA4) elicited survival benefits in cancer patients; however, the overall response rate is limited. In addition, anti-CTLA4 antibody therapy induces a high rate of immune-related adverse events. The underlying factors that may influence anti-CTLA4 antibody therapy are not well defined. We report the impact of a cancer-derived immune modulator, the human-soluble natural killer group 2D (NKG2D) ligand sMIC (soluble major histocompatibility complex I chain-related molecule), on the therapeutic outcome of anti-CTLA4 antibody using an MIC transgenic spontaneous TRAMP (transgenic adenocarcinoma of the mouse prostate)/MIC tumor model...
May 2017: Science Advances
https://www.readbyqxmd.com/read/28559451/a-disease-linked-ulbp6-polymorphism-inhibits-nkg2d-mediated-target-cell-killing-by-enhancing-the-stability-of-nkg2d-ligand-binding
#17
Jianmin Zuo, Carrie R Willcox, Fiyaz Mohammed, Martin Davey, Stuart Hunter, Kabir Khan, Ayman Antoun, Poonam Katakia, Joanne Croudace, Charlotte Inman, Helen Parry, David Briggs, Ram Malladi, Benjamin E Willcox, Paul Moss
NKG2D (natural killer group 2, member D) is an activating receptor found on the surface of immune cells, including natural killer (NK) cells, which regulates innate and adaptive immunity through recognition of the stress-induced ligands ULBP1 (UL16 binding protein 1) to ULBP6 and MICA/B. Similar to class I human leukocyte antigen (HLA), these NKG2D ligands have a major histocompatibility complex-like fold and exhibit pronounced polymorphism, which influences human disease susceptibility. However, whereas class I HLA polymorphisms occur predominantly in the α1α2 groove and affect antigen binding, the effects of most NKG2D ligand polymorphisms are unclear...
May 30, 2017: Science Signaling
https://www.readbyqxmd.com/read/28559450/new-connections-manipulating-nk-cell-responses
#18
John F Foley
Manipulating ligand interactions with the activating receptor NKG2D modulates natural killer cell responses.
May 30, 2017: Science Signaling
https://www.readbyqxmd.com/read/28550492/microrna-889-is-downregulated-by-histone-deacetylase-inhibitors-and-confers-resistance-to-natural-killer-cytotoxicity-in-hepatocellular-carcinoma-cells
#19
Haitao Xie, Qiugui Zhang, Hui Zhou, Jun Zhou, Ji Zhang, Yan Jiang, Jinghong Wang, Xianglin Meng, Leping Zeng, Xiaoxin Jiang
Major histocompatibility complex class I chain-related gene B (MICB) is expressed on tumor cells and participates in natural killer (NK) cell-mediated antitumor immune response through engagement with the NKG2D receptor. This study was undertaken to identify novel microRNA (miRNA) regulators of MICB and clarify their functions in NK cell-mediated cytotoxicity to hepatocellular carcinoma (HCC) cells. Bioinformatic analysis and luciferase reporter assay were conducted to search for MICB-targeting miRNAs. Overexpression and knockdown experiments were performed to determine the roles of candidate miRNAs in the susceptibility of HCC cells to NK lysis...
May 26, 2017: Cytotechnology
https://www.readbyqxmd.com/read/28549488/microwave-induced-apoptosis-and-cytotoxicity-of-nk-cells-through-erk1-2-signaling
#20
Li Zhao, Jing Li, Yan Hui Hao, Ya Bing Gao, Shui Ming Wang, Jing Zhang, Ji Dong, Hong Mei Zhou, Shu Chen Liu, Rui Yun Peng
OBJECTIVE: To investigate microwave-induced morphological and functional injury of natural killer (NK) cells and uncover their mechanisms. METHODS: NK-92 cells were exposed to 10, 30, and 50 mW/cm2 microwaves for 5 min. Ultrastructural changes, cellular apoptosis and cell cycle regulation were detected at 1 h and 24 h after exposure. Cytotoxic activity was assayed at 1 h after exposure, while perforin and NKG2D expression were detected at 1 h, 6 h, and 12 h after exposure...
May 2017: Biomedical and Environmental Sciences: BES
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