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Natural killer cells

Miok Kim, Seon-Jin Lee, Sangsu Shin, Kang-Seo Park, Sang Yoon Park, Chang Hoon Lee
Despite advances in the clinical management of hepatocellular carcinoma (HCC), this form of cancer remains the second leading cause of cancer-related death worldwide. Currently, there are few treatment options for advanced HCC. Therefore, novel treatment strategies for HCC are required. Here, we described the promising antitumour effects of anisomycin, which exerts both direct killing effects and natural killer cell (NK)-mediated immunotherapeutic effects in HCC. To better elucidate the mechanisms through which anisomycin mediates its antitumour effects, we performed a genome-scale transcriptional analysis...
July 13, 2018: Scientific Reports
(no author information available yet)
Natural killer (NK) cell interactions with stimulatory dendritic cells (SDC) enhance immunotherapy.
July 13, 2018: Cancer Discovery
Zhikuan Chen, Lanlan Liu, Ruijing Liang, Zhenyu Luo, Huamei He, Zhihao Wu, Hao Tian, Mingbin Zheng, Yifan Ma, Lintao Cai
An ideal cancer therapeutic strategy is expected to possess potent ability that not only can ablate primary tumor, but also can prevent the distance metastasis and relapse. In this study, human serum albumin was hybridized with hemoglobin by intermolecular disulfide bonds to develop a hybrid protein oxygen nanocarrier with chlorine e6 encapsulated (C@HPOC) for oxygen self-sufficient photodynamic therapy (PDT). C@HPOC realized the tumor-targeted co-delivery of photosensitizer and oxygen, which remarkably relieved tumor hypoxia...
July 13, 2018: ACS Nano
Rossella Sartorius, Luciana D'Apice, Pasquale Barba, Deborah Cipria, Laura Grauso, Adele Cutignano, Piergiuseppe De Berardinis
We have exploited the properties of filamentous bacteriophage fd to deliver immunologically active lipids together with antigenic peptides. Filamentous bacteriophages resemble for size, capability to be permeable to blood vessels, and high density antigen expression, a nature-made nanoparticle. In addition, their major coat protein pVIII, which is arranged to form a tubular shield surrounding the phage genome, has a high content of hydrophobic residues promoting lipid association. We conjugated bacteriophages to alpha-GalactosylCeramide (α-GalCer), a lipid antigen-stimulating invariant natural killer T (iNKT) cells and capable of inducing their anti-tumoral activities...
2018: Frontiers in Immunology
Li Chen, Yundong Wei, Shimei Zhao, Mengliang Zhang, Xiaoting Yan, Xiangyun Gao, Jinxia Li, Yutong Gao, Anwen Zhang, Ying Gao
Persimmon (Diospyros kaki L.) leaves are commonly used in Asia as tea infusion and as an agent in traditional medicine. The present study aims to explore the antitumor and immunomodulatory effects of total flavonoids extract from persimmon leaves (PLF) in H22 liver tumor-bearing mice. We found that the PLF showed significant inhibition on the liver tumor growth in mice with a tumor inhibition rate of up to 49.35%. In contrast to the severe side effects of cyclophosphamide (CTX), the PLF exhibited anti-cachexia effect and showed no alternation in the body weight and food intake in mice...
July 12, 2018: Scientific Reports
Fevzi Firat Yalniz, Naval Daver, Katayoun Rezvani, Steven Kornblau, Maro Ohanian, Gautam Borthakur, Courtney D DiNardo, Marina Konopleva, Jan Burger, Yvonne Gasior, Sherry Pierce, Hagop Kantarjian, Guillermo Garcia-Manero
BACKGROUND: Enhancement of natural killer cell activity by blocking interactions between killer immunoglobulin (Ig)-like receptors (KIRs) and human leukocyte antigen-C (HLA-C) molecules can improve outcomes in myeloid malignancies. Lirilumab is a human IgG4 monoclonal antibody that blocks KIR/HLA-C interaction. We designed a study to evaluate the safety and efficacy of lirilumab as a single agent and in combination with azacitidine in patients with myelodysplastic syndrome (MDS). PATIENTS AND METHODS: Adult patients with MDS who had not received previous hypomethylating agents were included...
June 15, 2018: Clinical Lymphoma, Myeloma & Leukemia
Dan Xu, Xiaoyu Liu, Chengyang Lu, Jing Luo, Caihong Wang, Chong Gao, Jianfang Xie, Xiaofeng Li
OBJECTIVES: Little is known about the roles of peripheral immune cell subsets in synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome. Up to now, just a few studies have focused on this issue. We aimed to analyse the distribution and phenotype of T cell subsets and natural killer (NK) cells in the peripheral blood of patients with SAPHO syndrome. METHODS: The proportion and absolute counts of circulating immune cells were assessed in 19 patients diagnosed as SAPHO syndrome and 19 healthy controls...
June 25, 2018: Clinical and Experimental Rheumatology
Takeshi Nagamatsu, Tatsuya Fujii, Danny J Schust, Naoko Tsuchiya, Yohei Tokita, Mari Hoya, Naoya Akiba, Takayuki Iriyama, Kei Kawana, Yutaka Osuga, Tomoyuki Fujii
OBJECTIVE: Tokishakuyakusan (TSS) is a traditional herbal medicine that has been used empirically to prevent recurrent pregnancy loss. Its mode of action remains unclear. With their potent capacity to produce cytokines, invariant natural killer (iNKT) cells are involved in the control of fetomaternal immunity in early gestation. This study aimed to clarify the effect of TSS on iNKT cell activities in a well-studied murine miscarriage model. METHODS: Pregnant mice were fed 1% TSS-containing or control diet from the day of vaginal plug formation...
July 12, 2018: American Journal of Reproductive Immunology: AJRI
Motonobu Nomura, Masataka Tsuge, Takuro Uchida, Nobuhiko Hiraga, Mio Kurihara, Ken Tsushima, Hatsue Fujino, Takashi Nakahara, Eisuke Murakami, Hiromi Abe-Chayama, Tomokazu Kawaoka, Daiki Miki, Akira Hiramatsu, Michio Imamura, Yoshiiku Kawakami, Hiroshi Aikata, Hidenori Ochi, Yizhou Zhang, Grace Naswa Makokha, C Nelson Hayes, Shinji Tanaka, Kazuaki Chayama
The activation of hepatitis B virus (HBV)-related hepatitis is associated with both natural killer (NK) cells and cytotoxic T lymphocytes (CTLs). We analyzed the association between the immune response and changes in the proportion of Pre-S deletion variants. We quantified Pre-S deleted HBV (HBV-del) and wild type HBV (HBV-wt) DNA levels in sera obtained from HBV-infected mice and chronic hepatitis B patients. In chronic hepatitis B patients, the HBV-del proportion usually increased during or after ALT elevation but did not occur during all ALT elevations...
July 11, 2018: Journal of Viral Hepatitis
Haiguang Wang, Kristin A Hogquist
In contrast to peptide-recognizing T cells, invariant natural killer T (iNKT) cells express a semi-invariant T cell receptor that specifically recognizes self- or foreign-lipids presented by CD1d molecules. There are three major functionally distinct effector states for iNKT cells. Owning to these innate-like effector states, iNKT cells have been implicated in early protective immunity against pathogens. Yet, growing evidence suggests that iNKT cells play a role in tissue homeostasis as well. In this review, we discuss current knowledge about the underlying mechanisms that regulate the effector states of iNKT subsets, with a highlight on the roles of a variety of transcription factors and describe how each subset influences different facets of thymus homeostasis...
2018: Frontiers in Immunology
J Lu, J Li, Q Y Han, X X Lu, Y Hu, H C Chen, J Hu
Objective: To preliminary analysis of the characteristics of lymphocyte subsets in peripheral blood among 135 cases of coal worker's pneumoconiosis patients in Huainan mining area. Methods: The peripheral bloods of 135 cases of coal worker's pneumoconiosis patients and 112 cases of health examiners were collected. Flow cytometry was used to detect peripheral blood lymphocytes, T cell subsets and CD4(+)CD25(+) regulatory T cells. Results: Compared with the control group, CD64 index of granulocytes and lymphocytes was slightly higher...
May 20, 2018: Chinese Journal of Industrial Hygiene and Occupational Diseases
Jie Geng, Anita J Zaitouna, Malini Raghavan
Major histocompatibility complex class I (MHC-I) molecules present antigenic peptides to CD8+ T cells, and are also important for natural killer (NK) cell immune surveillance against infections and cancers. MHC-I molecules are assembled via a complex assembly pathway in the endoplasmic reticulum (ER) of cells. Peptides present in the cytosol of cells are transported into the ER via the transporter associated with antigen processing (TAP). In the ER, peptides are assembled with MHC-I molecules via the peptide-loading complex (PLC)...
July 11, 2018: PLoS Pathogens
Takahiro Uchida, Hiroyuki Nakashima, Seigo Ito, Takuya Ishikiriyama, Masahiro Nakashima, Shuhji Seki, Hiroo Kumagai, Naoki Oshima
Although activation of mouse natural killer T (NKT) cells by alpha-galactosylceramide (α-GalCer) causes failure of multiple organs, including the kidneys, precise mechanisms underlying kidney injury remain unclear. Here, we showed that α-GalCer-activated mouse NKT cells injured both kidney vascular endothelial cells and tubular epithelial cells in vitro, causing acute kidney injury (AKI) with hematuria in middle-aged mice. Perforin-mediated pathway was mainly involved in glomerular endothelial cell injury, whereas TNF-α/Fas ligand pathway played an important role in the injury of tubular epithelial cells...
July 11, 2018: American Journal of Physiology. Renal Physiology
Nianqiu Liu, Bin Liu, Li Zhang, Hu Li, Zhiwei Chen, Aoran Luo, Min Chen, Mingli Peng, Wenwei Yin, Hong Ren, Peng Hu
BACKGROUND AND AIMS: Much evidence indicates that the soluble antigens secreted by hepatitis B virus (HBV) inhibit the function of the immune system. The aim of this study is to investigate, after treatment with nucleoside (acid) analogs (NAs) and the inhibition of viral replication, whether the immune systems of patients with a peripheral blood HBV-DNA level <1000 IU/mL, hepatitis B e antigen (HBeAg) disappearance, and a decrease in hepatitis B surface antigen (HBsAg) levels could be reconstructed...
July 4, 2018: International Immunopharmacology
Gregory T Wolf, Jeffrey S Moyer, Michael J Kaplan, Jason G Newman, James E Egan, Neil L Berinstein, Theresa L Whiteside
Head and neck squamous cell carcinoma (HNSCC) is an immunosuppressive malignancy characterized by tumor-driven immune-system abnormalities that contribute to disease progression. For patients with surgically resectable HNSCC, treatment is often curative surgery followed by irradiation or chemoradiation in high-risk settings to reduce the risk of recurrence. Poor survival and considerable morbidity of current treatments suggest the need for new therapeutic modalities that can improve outcomes. Defects in antitumor immunity of HNSCC patients include suppressed dendritic cell (DC) maturation, deficient antigen-presenting cell function, compromised natural killer (NK)-cell cytotoxicity, increased apoptosis of activated T lymphocytes, and impaired immune-cell migration to tumor sites...
2018: OncoTargets and Therapy
Xiang Fang, Muhammad Haidar Zaman, Xuanxuan Guo, Huimin Ding, Changhao Xie, Xiaojun Zhang, Guo-Min Deng
The onset of hepatic disorders in patients with systemic lupus erythematosus (SLE) is frequent; however, the etiology and liver pathogenesis of SLE remain unknown. In the present study, the role of hepatic deposited immunoglobulin G (IgG) in SLE-derived liver damage was investigated. From a retrospective analysis of the medical records of 404 patients with lupus and from experimental studies on mice models, we found that liver dysfunction is common in SLE and liver damage with IgG deposition spontaneously develops in lupus-prone mice...
2018: Frontiers in Immunology
Niken M Mahaweni, Femke A I Ehlers, Subhashis Sarkar, Johanna W H Janssen, Marcel G J Tilanus, Gerard M J Bos, Lotte Wieten
Natural killer (NK) cell-based immunotherapy is a promising therapy for cancer patients. Inhibitory killer immunoglobulin-like receptors (KIRs) and NKG2A are required for NK cell licensing, but can also inhibit NK cell effector function. Upon reconstitution in a stem cell transplantation setting or after ex vivo NK expansion with IL-2, NKG2A is expressed on a large percentage of NK cells. Since the functional consequences of NKG2A co-expression for activated NK cells are not well known, we compared NKG2A+ vs NKG2A- NK cell subsets in response to K562 cells, multiple myeloma (MM) cell lines and primary MM cells...
2018: Frontiers in Immunology
María Soledad Caldirola, María Guadalupe Rodríguez Broggi, María Isabel Gaillard, Liliana Bezrodnik, Norberto Walter Zwirner
Natural killer (NK) cells play a pivotal role during immunity against viruses and circumstantial evidence also indicates that they can protect the host against developing tumors. Peripheral blood NK cells comprise CD56bright CD16lo/- cells that constitutively express CD25 (IL-2Rα) and CD56dim CD16hi cells that express CD25 upon activation. Using NK cells from two patients, one with a primary immunodeficiency characterized by a homozygous mutation in CD25 (born in year 2007 and studied since she was 3 years old) and one with a homozygous mutation in STAT5b (born in year 1992 and studied since she was 10 years old), we observed that the absence of IL-2 signaling through CD25 promotes the accumulation of CD56bright CD16high NK cells, and that CD56bright CD16lo , CD56bright CD16high , and CD56dim CD16high NK cells of this patient exhibited higher content of perforin and granzyme B, and proliferation capacity, compared to healthy donors...
2018: Frontiers in Immunology
Paola Rivera-Munoz, Anouchka P Laurent, Aurelie Siret, Cecile K Lopez, Cathy Ignacimouttou, Melanie G Cornejo, Olivia Bawa, Philippe Rameau, Olivier A Bernard, Philippe Dessen, Gary D Gilliland, Thomas Mercher, Sébastien Malinge
JAK3-activating mutations are commonly seen in chronic or acute hematologic malignancies affecting the myeloid, megakaryocytic, lymphoid, and natural killer (NK) cell compartment. Overexpression models of mutant JAK3 or pharmacologic inhibition of its kinase activity have highlighted the role that these constitutively activated mutants play in the T-cell, NK cell, and megakaryocytic lineages, but to date, the functional impact of JAK3 mutations at an endogenous level remains unknown. Here, we report a JAK3A572V knockin mouse model and demonstrate that activated JAK3 leads to a progressive and dose-dependent expansion of CD8+ T cells in the periphery before colonization of the bone marrow...
July 10, 2018: Blood Advances
Timothy B Fessenden, Ellen Duong, Stefani Spranger
Recent work by Böttcher and colleagues defines a new role for Natural Killer cells in the anti-tumor immune response, arriving early into the tumor microenvironment before passing the baton to DC1 dendritic cells. DC1 dendritic cells subsequently activate CD8+ T cells resulting in effective anti-tumor immunity. This work highlights the cooperative nature of anti-tumor immunity set in motion by Natural Killer cells, and immune evasion by tumors through their exclusion.
July 9, 2018: Journal for Immunotherapy of Cancer
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