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Dongfang Wang, Xiuling Gu, Xiaoman Liu, Songtao Wei, Bin Wang, Min Fang
Tuberculosis remains a threat to public health. The major problem for curing this disease is latent infection, of which the underlying mechanisms are still not fully understood. Previous studies indicate that NK cells do not play a role in inhibiting the growth of Mycobacterium tuberculosis in the lung, and recent studies have revealed that NK cells regulate the adaptive immunity during mycobacterial infection. By using a mouse model of direct lung infection with M.bovis BCG, we found that the presence of NK cells postponed the priming and activation of T cells after BCG infection...
February 15, 2018: Cellular Microbiology
Eline Haspeslagh, Mary J van Helden, Kim Deswarte, Sofie De Prijck, Justine van Moorleghem, Louis Boon, Hamida Hammad, Eric Vivier, Bart N Lambrecht
House dust mite (HDM)-allergic asthma is driven by T helper 2 (Th2) lymphocytes, but also innate immune cells control key aspects of the disease. The precise function of innate natural killer (NK) cells during the initiation and propagation of asthma has been very confusing, in part because different, not entirely specific, strategies were used to target these cells. We show that HDM inhalation rapidly led to the accumulation of NK cells in the lung-draining lymph nodes and of activated CD69 + NK cells in the bronchoalveolar lumen...
February 14, 2018: EMBO Molecular Medicine
J Luis Espinoza, Mika Minami
The human genome is constantly exposed to exogenous and endogenous DNA damaging factors that frequently cause DNA damages. Unless repaired, damaged DNA can result in deleterious mutations capable of causing malignant transformation. Accordingly, cells have developed an advanced and effective surveillance system, the DNA damage response (DDR) pathway, which maintains genetic integrity. In addition to well-defined outcomes, such as cell cycle arrest, apoptosis, and senescence, another consequence of DDR activation is the induction of natural killer group 2 member D ligands (NKG2D-Ls) on the surface of stressed cells...
2018: Frontiers in Immunology
Lijun Xu, Mingjing Shen, Xiaodong Chen, Dong-Rong Yang, Ying Tsai, Peter C Keng, Soo Ok Lee, Yuhchyau Chen
Previous reports, including our experimental results, showed that macrophages migrate to prostate cancer (PCa) cells. We tested whether the migrated macrophages affect the susceptibility of castration-resistant PCa (CRPC) cells to cytotoxic actions of natural killer (NK) cells. We found treatment of tumor cells with the conditioned media (CM) of the PMA/IL-4 treated THP-1 cells (M2 type macrophages) (THP-1 CM) decreased the susceptibility of tumor cells to NK cell cytotoxicity, as a result of increased programmed death receptor ligand 1 (PD-L1) and decreased NK group 2D (NKG2D) ligands in CRPC cells...
January 31, 2018: Experimental Cell Research
M Gharagozloo, A Rezaei, H Kalantari, A Bahador, N Hassannejad, M Maracy, N Nouri, M Sedghi, H Ghazanfari, B Bayat
OBJECTIVE: Colorectal cancer (CRC) is one of the main causes of cancer deaths in the world. This cancer can be divided into non-metastatic and metastatic CRC stages. CD3+CD56+ NKT cell subsets are a minor T cell subset in peripheral blood and conduct the killing of tumor cells in direct manner. Little is obvious about levels and surface markers of these cells such as NKG2D in different cancers, especially in CRC. METHODS: We included 15 non-metastatic (low-grade), 11 non-metastatic (high-grade), 10 metastatic colorectal cancer patients and 18 healthy controls...
2018: Bratislavské Lekárske Listy
Kushal Prajapati, Cynthia Perez, Lourdes Beatriz Plaza Rojas, Brianna Burke, Jose A Guevara-Patino
Natural killer group 2 member D (NKG2D) is a type II transmembrane receptor. NKG2D is present on NK cells in both mice and humans, whereas it is constitutively expressed on CD8+ T cells in humans but only expressed upon T-cell activation in mice. NKG2D is a promiscuous receptor that recognizes stress-induced surface ligands. In NK cells, NKG2D signaling is sufficient to unleash the killing response; in CD8+ T cells, this requires concurrent activation of the T-cell receptor (TCR). In this case, the function of NKG2D is to authenticate the recognition of a stressed target and enhance TCR signaling...
February 5, 2018: Cellular & Molecular Immunology
Mark Bazett, Amanda M Costa, Momir Bosiljcic, Rebecca M Anderson, Matthew P Alexander, Stephanie W Y Wong, Salim Dhanji, Jenny Mh Chen, Jim Pankovich, Stephen Lam, Simon Sutcliffe, Hal Gunn, Shirin Kalyan, David W Mullins
Acute infection is known to induce strong anti-tumor immune responses, but clinical translation has been hindered by the lack of an effective strategy to safely and consistently provoke a therapeutic response. These limitations are overcome with a novel treatment approach involving repeated subcutaneous delivery of a Klebsiella-derived investigational immunotherapeutic, QBKPN. In preclinical models of lung cancer, QBKPN administration consistently showed anti-cancer efficacy, which was dependent on Klebsiella pre-exposure, but was independent of adaptive immunity...
2018: Oncoimmunology
Rika Fujii, Caroline Jochems, Sarah R Tritsch, Hing C Wong, Jeffrey Schlom, James W Hodge
Natural killer (NK) cells are innate cytotoxic lymphocytes that play a fundamental role in the immunosurveillance of cancers. NK cells of cancer patients exhibit impaired function mediated by immunosuppressive factors released from the tumor microenvironment (TME), such as transforming growth factor (TGF)-β1. An interleukin (IL)-15 superagonist/IL-15 receptor α fusion complex (IL-15SA/IL-15RA; ALT-803) activates the IL-15 receptor on CD8 T cells and NK cells, and has shown significant anti-tumor activity in several in vivo studies...
February 1, 2018: Cancer Immunology, Immunotherapy: CII
Hyung Gun Maeng, Su Jin Lee, Yun A Lee, Hye Jeong Lee, Young Joo Kim, Jong Kyun Lee, Jae Cheol Kim, Joungbum Choi
Cytotoxicity assays with patient peripheral blood mononuclear cell (PBMC)-derived natural killer (NK) cells are useful in evaluating the innate immunity of patients with cancer. However, the size of the NK cell population in PBMC preparations may have significant effects on the assay outcome. Therefore, the present study examined the effect of NK cell frequency in a cytotoxicity system to investigate NK cell immunity in post-surgical colorectal cancer patients. For this, hemacytotoxicity was assessed using PBMC preparations, and lymphocyte subset populations were analyzed in samples obtained from 47 patients and 45 healthy volunteers...
January 2018: Oncology Letters
Ryoji Kamei, Kiyoshi Yoshimura, Shigefumi Yoshino, Moeko Inoue, Tetsuhiko Asao, Masanori Fuse, Satoshi Wada, Atsuo Kuramasu, Tomoko Furuya-Kondo, Atsunori Oga, Norio Iizuka, Nobuaki Suzuki, Noriko Maeda, Yusaku Watanabe, Satoshi Matsukuma, Michihisa Iida, Shigeru Takeda, Tomio Ueno, Noboru Yamamoto, Takeo Fukagawa, Hitoshi Katai, Hiroki Sasaki, Shoichi Hazama, Masaaki Oka, Hiroaki Nagano
UL16 binding protein 1 (ULBP1) expressed on the tumor cell surface binds to the natural killer group 2 member D (NKG2D) receptor presenting on natural killer (NK), cluster of differentiation (CD)8+ T, and γ δ T cells. However, the roles of ULBP1 and NKG2D expression and associated immune responses in gastric cancer are unclear. The present study investigated the associations between ULBP1 and NKG2D expression and clinical outcomes in patients with gastric cancer. The levels of ULBP1 and NKG2D expression were examined in human gastric cancer cell lines and gastric cancer tissues from 98 patients who underwent surgery from 2004 to 2008...
January 2018: Oncology Letters
Jiemiao Hu, Chuang Sun, Chantale Bernatchez, Xueqing Xia, Patrick Hwu, Gianpietro Dotti, Shulin Li
PURPOSE: Infused autologous tumor-infiltrating lymphocytes (TILs) and tumor-targeted chimeric antigen receptor (CAR)-T cells typically surround malignant lesions or penetrate small tumor nodules, but fail to penetrate large solid tumors, significantly compromising their antitumor impact. Strategies to overcome this primary challenge are largely required. EXPERIMENTAL DESIGN: We tested the effects of IL-12 plus doxorubicin on T cell penetration and efficacy in solid tumors in a murine lung cancer model, a murine breast carcinoma lung metastasis model and two human xenograft tumor models bearing large tumors (>10 mm)...
February 1, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Takeshi Ishikawa, Tetsuya Okayama, Naoyuki Sakamoto, Mitsuko Ideno, Kaname Oka, Tatsuji Enoki, Junichi Mineno, Naohisa Yoshida, Kazuhiro Katada, Kazuhiro Kamada, Kazuhiko Uchiyama, Osamu Handa, Tomohisa Takagi, Hideyuki Konishi, Satoshi Kokura, Kazuko Uno, Yuji Naito, Yoshito Itoh
Natural killer (NK) cells exhibit strong cytotoxic activity against tumor cells without prior sensitization, and have the potential to exert antibody-dependent cellular cytotoxicity (ADCC). In this clinical trial, we examined the safety and efficacy of the use of NK cells, generated using a novel expansion system, in combination with IgG1 antibodies for the treatment of advanced gastric or colorectal cancers. Treatment consisted of trastuzumab- or cetuximab-based chemotherapy, plus adoptive NK cell therapy...
January 31, 2018: International Journal of Cancer. Journal International du Cancer
Milena Iwaszko, Jerzy Świerkot, Katarzyna Kolossa, Sławomir Jeka, Piotr Wiland, Katarzyna Bogunia-Kubik
A natural killer group 2 member D (NKG2D) acts as a powerful activating and co-stimulatory receptor on immune effector cells including NK and T cells. Disruptions within the NKG2D signalling pathway may trigger an exacerbated immune response and promote autoimmune reactions. The objective of the study was to evaluate a plausible role of polymorphisms within the NKG2D gene as a predictor of how effective anti-tumor necrosis factor (TNF) therapy is in rheumatoid arthritis (RA) patients. A total of 280 RA patients receiving anti-TNF therapy were genotyped for NKG2D rs2255336 (A > G), rs1049174 (C > G), and rs1154831 (C > A)...
January 25, 2018: Genes
Martino Introna, Fabio Correnti
Cytokine-induced killer (CIK) cells are T lymphocytes that have acquired, in vitro, following extensive manipulation by Interferon gamma (IFN-γ), OKT3 and Interleukin 2 (IL-2) addition, the expression of several Natural Killer (NK) cell-surface markers. CIK cells have a dual "nature", due to the presence of functional TCR as well as NK molecules, even if the antitumoral activity can be traced back only to the NK-like structures (DNAM-1, NKG2D, NKp30 and CD56). In addition to antineoplastic activity in vitro and in several in-vivo models, CIK cells show very limited, if any, GvHD toxicity as well as a strong intratumoral homing...
January 25, 2018: International Journal of Molecular Sciences
Yu Uemura, Yasushi Isobe, Akiko Uchida, Junko Asano, Yuji Nishio, Hirotaka Sakai, Masahiro Hoshikawa, Masayuki Takagi, Naoya Nakamura, Ikuo Miura
Peripheral T- or NK-cell lymphomas are rare and difficult-to-recognize diseases. It remains arduous to distinguish between NK cell- and cytotoxic T lymphocyte-derived lymphomas through routine histologic evaluation. To clarify the cells of origin, we focused on NK-cell receptors and examined the expression using immunohistochemistry in 22 cases with T- and NK-cell neoplasms comprising of angioimmunoblastic T-cell lymphoma, ALK-positive and -negative anaplastic large cell lymphomas, extranodal NK/T-cell lymphoma, nasal type, monomorphic epitheliotropic intestinal T-cell lymphoma, aggressive NK-cell leukemia, and other peripheral T-cell lymphomas...
January 24, 2018: Cancer Science
Sofya A Erokhina, Maria A Streltsova, Leonid M Kanevskiy, William G Telford, Alexander M Sapozhnikov, Elena I Kovalenko
NK cells change their phenotype and functional characteristics during activation. In this work, we searched for a relationship of HLA-DR expression with differentiation stages and functional activity of NK cells ex vivo and stimulated in vitro with IL-2 challenged with gene modified feeder K562 cells expressing membrane-bound IL-21 (K562-mbIL21). This stimulation technique has been described for NK cell expansion in clinical use. We have observed that HLA-DR expression in freshly isolated circulating NK cells was mostly associated with less differentiated CD56bright CD57- cells, although in some individuals it could also be found in terminally differentiated CD57+ cells...
November 22, 2017: Immunology and Cell Biology
Neidy Varela Rodrigues, Daniel V Correia, Sofia Mensurado, Sandrina Nobrega-Pereira, Ana deBarros, Fernanda Kyle-Cezar, Andrew Tutt, Adrian C Hayday, Haakan Norell, Bruno Silva-Santos, Sergio Dias
Vgamma9Vdelta2 T cells, the main subset of gamma delta T lymphocytes in human peripheral blood, are endowed with antitumor functions such as cytotoxicity and IFNgamma production. These functions are triggered upon TCR-dependent activation by non-peptidic prenyl pyrophosphates ("phosphoantigens") that are selective agonists of Vgamma9Vdelta2 T cells, and which have been evaluated in clinical studies. Because phosphoantigens have shown inter-individual variation in Vgamma9Vdelta2 T-cell activities, we asked whether metabolic resources, namely lipids such as cholesterol, could affect phosphoantigen-mediated Vgamma9Vdelta2 T-cell activation and function...
January 22, 2018: Cancer Immunology Research
Charlotte Flüh, Guranda Chitadze, Vivian Adamski, Kirsten Hattermann, Michael Synowitz, Dieter Kabelitz, Janka Held-Feindt
Glioblastoma multiforme (GBM) is a highly malignant brain tumor. Tumor stem cells have a major influence on tumor malignancy, and immunological escape mechanisms, involving the Natural Killer Group 2, member D (NKG2D) receptor-ligand-system, are key elements in tumor immuno-surveillance. We analyzed the expression profile and localization of NKG2D ligands (NKG2DL) and embryonic and neural stem cell markers in solid human GBM and stem-like cells isolated from glioma cell lines by qRT-PCR and immunohistochemistry, including quantitative analysis...
January 22, 2018: Histochemistry and Cell Biology
T Y He, Y Xia, C G Li, C R Li, Z X Qi, J Yang
Objective: To investigate the clinical features and genetic characteristics of cases with X-linked immunodeficiency with magnesium defect, Epstein-Barr virus (EBV) infection, and neoplasia (XMEN). Methods: Characteristics of clinical material, immunological data and gene mutation of two cases with XMEN in the same family in China were retrospectively analyzed. The related reports literature were searched by using search terms'MAGT1 gene'or'XMEN'. Results: The proband, a 2-year-eight-month old boy, was admitted due to 'Urine with deepened color for two days and yellow stained skin for one day'...
January 2, 2018: Zhonghua Er Ke za Zhi. Chinese Journal of Pediatrics
Folashade Otegbeye, Evelyn Ojo, Stephen Moreton, Nathan Mackowski, Dean A Lee, Marcos de Lima, David N Wald
Natural killer cells harnessed from healthy individuals can be expanded ex vivo using various platforms to produce large doses for adoptive transfer into cancer patients. During such expansion, NK cells are increasingly activated and more efficient at killing cancer cells. Adoptive transfer however introduces these activated cells into a highly immunosuppressive tumor microenvironment mediated in part by excessive transforming growth factor beta (TGF-beta) from both cancer cells and their surrounding stroma...
2018: PloS One
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