22
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Hepatic Natural Killer Cells: Organ-Specific Sentinels of Liver Immune Homeostasis and Physiopathology

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          The liver is considered a preferential tissue for NK cells residency. In humans, almost 50% of all intrahepatic lymphocytes are NK cells that are strongly imprinted in a liver-specific manner and show a broad spectrum of cellular heterogeneity. Hepatic NK (he-NK) cells play key roles in tuning liver immune response in both physiological and pathological conditions. Therefore, there is a pressing need to comprehensively characterize human he-NK cells to better understand the related mechanisms regulating their effector-functions within the dynamic balance between immune-tolerance and immune-surveillance. This is of particular relevance in the liver that is the only solid organ whose parenchyma is constantly challenged on daily basis by millions of foreign antigens drained from the gut. Therefore, the present review summarizes our current knowledge on he-NK cells in the light of the latest discoveries in the field of NK cell biology and clinical relevance.

          Related collections

          Most cited references99

          • Record: found
          • Abstract: found
          • Article: not found

          Up on the tightrope: natural killer cell activation and inhibition.

          Natural killer (NK) cells circulate through the blood, lymphatics and tissues, on patrol for the presence of transformed or pathogen-infected cells. As almost all NK cell receptors bind to host-encoded ligands, signals are constantly being transmitted into NK cells, whether they interact with normal or abnormal cells. The sophisticated repertoire of activating and inhibitory receptors that has evolved to regulate NK cell activity ensures that NK cells protect hosts against pathogens, yet prevents deleterious NK cell-driven autoimmune responses. Here I highlight recent advances in our understanding of the structural properties and signaling pathways of the inhibitory and activating NK cell receptors, with a particular focus on the ITAM-dependent activating receptors, the NKG2D-DAP10 receptor complexes and the CD244 receptor system.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: found
            Is Open Access

            Anti-NKG2A mAb Is a Checkpoint Inhibitor that Promotes Anti-tumor Immunity by Unleashing Both T and NK Cells

            Summary Checkpoint inhibitors have revolutionized cancer treatment. However, only a minority of patients respond to these immunotherapies. Here, we report that blocking the inhibitory NKG2A receptor enhances tumor immunity by promoting both natural killer (NK) and CD8+ T cell effector functions in mice and humans. Monalizumab, a humanized anti-NKG2A antibody, enhanced NK cell activity against various tumor cells and rescued CD8+ T cell function in combination with PD-x axis blockade. Monalizumab also stimulated NK cell activity against antibody-coated target cells. Interim results of a phase II trial of monalizumab plus cetuximab in previously treated squamous cell carcinoma of the head and neck showed a 31% objective response rate. Most common adverse events were fatigue (17%), pyrexia (13%), and headache (10%). NKG2A targeting with monalizumab is thus a novel checkpoint inhibitory mechanism promoting anti-tumor immunity by enhancing the activity of both T and NK cells, which may complement first-generation immunotherapies against cancer.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              In search of the ‘missing self’: MHC molecules and NK cell recognition

              Immunology Today, 11, 237-244
                Bookmark

                Author and article information

                Contributors
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                30 April 2019
                2019
                : 10
                : 946
                Affiliations
                [1] 1Unit of Clinical and Experimental Immunology, Humanitas Clinical and Research Center , Milan, Italy
                [2] 2Department of Medical Biotechnologies and Translational Medicine, University of Milan , Milan, Italy
                Author notes

                Edited by: Simona Sivori, University of Genoa, Italy

                Reviewed by: Rafael Solana, Universidad de Córdoba, Spain; Daniela Pende, Ospedale San Martino (IRCCS), Italy

                *Correspondence: Domenico Mavilio domenico.mavilio@ 123456unimi.it

                This article was submitted to NK and Innate Lymphoid Cell Biology, a section of the journal Frontiers in Immunology

                Article
                10.3389/fimmu.2019.00946
                6502999
                31114585
                f6b6f320-2c5f-449c-85e2-f40c7a6bc41e
                Copyright © 2019 Mikulak, Bruni, Oriolo, Di Vito and Mavilio.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 01 February 2019
                : 12 April 2019
                Page count
                Figures: 3, Tables: 1, Equations: 0, References: 153, Pages: 12, Words: 10507
                Funding
                Funded by: Associazione Italiana per la Ricerca sul Cancro 10.13039/501100005010
                Funded by: Ministero della Salute 10.13039/501100003196
                Categories
                Immunology
                Review

                Immunology
                tissue immunity,liver,natural kill cell,homeostais,homeostasis
                Immunology
                tissue immunity, liver, natural kill cell, homeostais, homeostasis

                Comments

                Comment on this article