40 results found
Curio S, Edwards SC, Suzuki T, et al., 2022, NKG2D signaling regulates IL-17A-producing γδT cells in mice to promote cancer progression, Discovery Immunology, Vol: 1, ISSN: 2754-2483
γδT cells are unconventional T cells particularly abundant in mucosal tissues that play an important role in tissue surveillance, homeostasis and cancer. γδT cells recognize stressed cells or cancer cells through the NKG2D receptor to kill these cells and maintain normality. Contrary to the well-established anti-tumor function of these NKG2D-expressing γδT cells, we show here that, in mice, NKG2D regulates a population of pro-tumor γδT cells capable of producing IL-17A. Germline deletion of Klrk1, the gene encoding NKG2D, reduced the frequency of γδT cells in the tumor microenvironment and delayed tumor progression. We further show that blocking NKG2D reduced the capability of γδT cells to produce IL-17A in the pre-metastatic lung and that co-culture of lung T cells with NKG2D ligand-expressing tumor cells specifically increased the frequency of γδT cells. Together, these data support the hypothesis that in a tumor microenvironment where NKG2D ligands are constitutively expressed, γδT cells accumulate in an NKG2D-dependent manner and drive tumor progression by secreting pro-inflammatory cytokines, such as IL-17A.
Tomaz D, Pereira PM, Guerra N, et al., 2022, Nanoscale Colocalization of NK Cell Activating and Inhibitory Receptors Controls Signal Integration, FRONTIERS IN IMMUNOLOGY, Vol: 13, ISSN: 1664-3224
Cadoux M, Caruso S, Pham S, et al., 2021, Expression of NKG2D ligands is downregulated by β-catenin signalling and associates with HCC aggressiveness, JOURNAL OF HEPATOLOGY, Vol: 74, Pages: 1386-1397, ISSN: 0168-8278
Glymenaki M, Curio S, Cabrera PM, et al., 2021, TYRAMINE IS A POTENTIAL CONTRIBUTOR TO INCREASED COLON CANCER RISK FOLLOWING BARIATRIC SURGERY, Society-for-Surgery-of-the-Alimentary-Tract Annual Meeting at Digestive Disease Week (DDW), Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: S738-S738, ISSN: 0016-5085
Bonavita E, Bromley CP, Jonsson G, et al., 2020, Antagonistic Inflammatory Phenotypes Dictate Tumor Fate and Response to Immune Checkpoint Blockade, IMMUNITY, Vol: 53, Pages: 1215-+, ISSN: 1074-7613
Guerra N, Lanier LL, 2020, Editorial: Emerging Concepts on the NKG2D Receptor-Ligand Axis in Health and Diseases, FRONTIERS IN IMMUNOLOGY, Vol: 11, ISSN: 1664-3224
Pinato DJ, Guerra N, Fessas P, et al., 2020, Immune-based therapies for hepatocellular carcinoma, Oncogene, Vol: 39, Pages: 3620-3637, ISSN: 0950-9232
Hepatocellular carcinoma (HCC) is the third most frequent cause of cancer-related death. The immune-rich contexture of the HCC microenvironment makes this tumour an appealing target for immune-based therapies. Here, we discuss how the functional characteristics of the liver microenvironment can potentially be harnessed for the treatment of HCC. We will review the evidence supporting a therapeutic role for vaccines, cell-based therapies and immune-checkpoint inhibitors and discuss the potential for patient stratification in an attempt to overcome the series of failures that has characterised drug development in this disease area.
Cadoux M, Pham S, Caruso S, et al., 2019, Beta-catenin signaling controls NKG2D ligands expression in liver tumorigenesis, International Liver Congress / 54th Annual Meeting of the European-Association-for-the-Study-of-the-Liver (EASL), Publisher: ELSEVIER, Pages: E354-E355, ISSN: 0168-8278
The activating receptor NKG2D and its ligands are recognized as a potent immune axis that controls tumor growth and microbial infections. With regards to cancer surveillance, various studies have demonstrated the antitumor function mediated by NKG2D on natural killer cells and on conventional and unconventional T cells. The use of NKG2D-deficient mice established the importance of NKG2D in delaying tumor development in transgenic mouse models of cancer. However, we recently demonstrated an unexpected, flip side to this coin, the ability for NKG2D to contribute to tumor growth in a model of inflammation-driven liver cancer. With a focus on the liver, here, we review current knowledge of NKG2D-mediated tumor surveillance and discuss evidence supporting a dual role for NKG2D in cancer immunity. We postulate that in certain advanced cancers, expression of ligands for NKG2D can drive cancer progression rather than rejection. We propose that the nature of the microenvironment within and surrounding tumors impacts the outcome of NKG2D activation. In a form of autoimmune attack, NKG2D promotes tissue damage, mostly in the inflamed tissue adjacent to the tumor, facilitating tumor progression while being ineffective at rejecting transformed cells in the tumor bed.
Sheppard S, Schuster IS, Andoniou CE, et al., 2018, The murine natural cytotoxic receptor NKp46/NCR1 controls TRAIL protein expression in NK cells and ILC1, Cell Reports, Vol: 22, Pages: 3385-3392, ISSN: 2211-1247
TRAIL is an apoptosis-inducing ligand constitutively expressed on liver resident type 1 innate lymphoid cells (ILC1) and a subset of Natural Killer (NK) cells where it contributes to NK cell anti-tumor, anti-viral and immunoregulatory functions. Yet the intrinsic pathways involved in TRAIL expression in ILC remain unidentified. Here we demonstrate that the murine natural cytotoxic receptor mNKp46/NCR1, expressed on ILC1 and NK cells, controls TRAIL protein expression. Using NKp46-deficient mice, we show that liver ILC1 lack constitutive expression of TRAIL protein and that NK cells activated in vitro and in vivo fail to upregulate cell-surface TRAIL in the absence of NKp46. We show that NKp46 regulates TRAIL expression in a dose-dependent manner and that the reintroduction of NKp46 in mature NK cells deficient for NKp46 is sufficient to restore TRAIL surface expression. These studies uncover a link between NKp46 and TRAIL expression in ILC with potential implications in pathologies involving NKp46-expressing cells.
Sheppard S, Guedes J, Mroz A, et al., 2017, The immunoreceptor NKG2D promotes tumour growth in a model of hepatocellular carcinoma, Nature Communications, Vol: 8, ISSN: 2041-1723
Inflammation is recognized as one of the drivers of cancer. Yet, the individual immune components that possess pro- and anti-tumorigenic functions in individual cancers remain largely unknown. NKG2D is a potent activating immunoreceptor that has emerged as an important player in inflammatory disorders besides its well-established function as tumour suppressor. Here, we provide genetic evidence of an unexpected tumour-promoting effect of NKG2D in a model of inflammation-driven liver cancer. Compared to NKG2D-deficient mice, NKG2D-sufficient mice display accelerated tumour growth associated with, an increased recruitment of memory CD8(+)T cells to the liver and exacerbated pro-inflammatory milieu. In addition, we show that NKG2D contributes to liver damage and consequent hepatocyte proliferation known to favour tumorigenesis. Thus, the NKG2D/NKG2D-ligand pathway provides an additional mechanism linking chronic inflammation to tumour development in hepatocellular carcinoma. Our findings expose the need to selectively target the types of cancer that could benefit from NKG2D-based immunotherapy.
Collery P, Mohsen A, Kermagoret A, et al., 2015, Antitumor activity of a rhenium (I)-diselenoether complex in experimental models of human breast cancer, Investigational New Drugs, Vol: 33, Pages: 848-860, ISSN: 1573-0646
Rhenium (I)-diselenother (Re-diselenoether) is a water soluble metal-based compound, combining one atom of rhenium and two atoms of selenium. This compound has been reported to exhibit marked activities against several solid tumor cell lines. We now disclose an improved synthesis of this complex. The Re-diselenoether showed a potent inhibitory effect on MDA-MB231 cell division in vitro, which lasted when the complex was no longer present in the culture. Re-diselenoether induced a remarkable reduction of the volume of the primitive breast tumors and of the pulmonary metastases without clinical signs of toxicity, in mice-bearing a MDA-MB231 Luc+ tumor, orthotopically transplanted, after a daily oral administration at the dose of 10 mg/kg/d. Interestingly, an antagonism was observed when cisplatin was administered as a single i.p. injection 1 week after the end of the Re-diselenoether administration. In an effort to gain insight of the mechanisms of action of Re-diselenoether complex, interaction with 9-methylguanine as a nucleic acid base model was studied. We have shown that Re-diselenoether gave both mono- and bis-guanine Re adducts, the species assumed to be responsible for the DNA intrastrand lesions.
Sparks H, Warren S, Guedes J, et al., 2015, A flexible wide-field FLIM endoscope utilising blue excitation light for label-free contrast of tissue, JOURNAL OF BIOPHOTONICS, Vol: 8, Pages: 168-178, ISSN: 1864-063X
Basey-Fisher TH, Guerra N, Triulzi C, et al., 2014, Microwaving blood as a non‐destructive technique for haemoglobin measurements on microlitre samples, Advanced Healthcare Materials, Vol: 3, Pages: 536-542, ISSN: 2192-2640
The electric field component of the microwaves emanating from the dielectric resonator is able to penetrate the microfluidic channel, serum, and individual blood cells. Subsequently, it interacts with every hemoglobin molecule present within each red blood cell. On page 536 , Toby H. Basey-Fisher and team conclude that the dielectric contrast between water and hemoglobin means that a change in the hemoglobin concentration leads to a change in the microwave response.
Basey-Fisher TH, Guerra N, Triulzi C, et al., 2014, Microwaving Blood as a Non-Destructive Technique for Haemoglobin Measurements on Microlitre Samples, ADVANCED HEALTHCARE MATERIALS, Vol: 3, Pages: 536-542, ISSN: 2192-2640
Bio-sensing by electromagnetic waves from GHz towards THz frequencies, although not yet established as a common method for biomedical applications, offers challenging opportunities, which are complementary to the established optical methods, often based on plasmonic waves and resonances. The longer wavelength - in comparison to visible and IR provides a disadvantage in terms of the smallest possible interaction volume, which can be partially overcome by evanescent field methods. However, the high absorption of micro- and millimetre waves by liquid water, which is the most abundant component of biological substances, provides a unique observation window, which is substantially different and therefore complementary to the other parts of the electromagnetic spectrum. © 2013 IEEE.
Farhadi N, Lambert L, Triulzi C, et al., 2013, Natural Killer cell NKG2D and granzyme B are critical for allergic pulmonary inflammation, Journal of Allergy and Clinical Immunology
BackgroundThe diverse roles of innate immune cells in the pathogenesis of asthma remain to be fully defined. Natural killer (NK) cells are innate lymphocytes which can regulate adaptive immune responses. NK cells are activated in asthma; however, their role in allergic airway inflammation is not fully understood.ObjectiveWe investigated the importance of NK cells in house dust mite (HDM) triggered allergic pulmonary inflammation. Specifically, we aimed to determine the role of the major NK cell activating receptor NKG2D and NK cell effector functions mediated by granzyme B.MethodsAllergic airway inflammation was induced in the airways of mice by repeated intranasal HDM extract administration and responses in wild type and NKG2D deficient mice were compared. Adoptive transfer studies were used to identify the cells and mechanisms involved.ResultsMice lacking NKG2D were resistant to the induction of allergic inflammation and showed little pulmonary eosinophilia, few airway Th2 cells and no rise in serum IgE after multiple HDM allergen exposures. However, NKG2D was not required for pulmonary inflammation after a single inoculation of allergen. NKG2D deficient mice showed no alteration in responses to respiratory virus infection. Transfer of wild type NK cells (but not CD3+ cells) into NKG2D deficient mice restored allergic inflammatory responses only if the NK cells expressed granzyme B. ConclusionThese studies establish a pivotal role for NK cell NKG2D and granzyme B in the pathogenesis of HDM induced allergic lung disease, and identify novel therapeutic targets for the prevention and treatment of asthma.
Guerra N, Pestal K, Juarez T, et al., 2013, A selective role of NKG2D in inflammatory and autoimmune diseases, Clinical Immunology, ISSN: 1521-6616
Tomaz DT, Guerra N, Dyson JD, et al., 2013, Fluorescent tagged NK cell receptors expressed in vivo using retrogenic mice to study the delivery of signals in NK cells, International Congress of Immunology 2013
Guerra N, 2013, Fluorescent tagged NK cell receptors expressed in vivo using retrogenic mice to study the delivery of signals in NK cells, : International Congress of Immunology 2013
Sheppard S, Triulzi C, Ardolino M, et al., 2013, Characterization of a novel NKG2D and NKp46 double-mutant mouse reveals subtle variations in the NK cell repertoire, BLOOD, Vol: 121, Pages: 5025-5033, ISSN: 0006-4971
Farhadi N, Guerra N, Openshaw PJ, et al., 2013, The Role Of Nk Cells In Allergic Inflammation Of The Lung, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 187, ISSN: 1073-449X
Klein N, Basey-Fisher TH, Otter WJ, et al., 2013, TOWARDS MICROWAVE AND MILLIMTER WAVE BIOSENSORS, International Kharkov Symposium on Physics and Engineering of Microwaves, Millimeter and Submillimeter Waves (MSMW), Publisher: IEEE, Pages: 509-+
Xia M, Guerra N, Sukhova GK, et al., 2011, Immune Activation Resulting From NKG2D/Ligand Interaction Promotes Atherosclerosis, CIRCULATION, Vol: 124, Pages: 2933-U419, ISSN: 0009-7322
Xia M, Yang K, Guerra N, et al., 2010, NKG2D/ligands-mediated immune activation promotes atherosclerosis, JOURNAL OF IMMUNOLOGY, Vol: 184, ISSN: 0022-1767
Raulet DH, Guerra N, 2009, Oncogenic stress sensed by the immune system: role of natural killer cell receptors, NATURE REVIEWS IMMUNOLOGY, Vol: 9, Pages: 568-580, ISSN: 1474-1733
Whang MI, Guerra N, Raulet DH, 2009, Costimulation of Dendritic Epidermal γδ T Cells by a New NKG2D Ligand Expressed Specifically in the Skin, JOURNAL OF IMMUNOLOGY, Vol: 182, Pages: 4557-4564, ISSN: 0022-1767
Guerra N, Tan YX, Joncker NT, et al., 2008, NKG2D-deficient mice are defective in tumor surveillance in models of spontaneous malignancy, IMMUNITY, Vol: 28, Pages: 571-580, ISSN: 1074-7613
Gati A, Da Rocha S, Guerra N, et al., 2004, Analysis of the natural killer mediated immune response in metastatic renal cell carcinoma patients, INTERNATIONAL JOURNAL OF CANCER, Vol: 109, Pages: 393-401, ISSN: 0020-7136
Gati A, Guerra N, Gaudin C, et al., 2003, CD158 receptor controls cytotoxic T-lymphocyte susceptibility to tumor-mediated activation-induced cell death by interfering with fas signaling, CANCER RESEARCH, Vol: 63, Pages: 7475-7482, ISSN: 0008-5472
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