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Nat Rev Drug Discov. 2019 Apr 9. doi: 10.1038/s41573-019-0025-4. [Epub ahead of print]

Therapeutic targeting of trained immunity.

Author information

1
Translational and Molecular Imaging Institute, Department of Radiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. willem.mulder@mssm.edu.
2
Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA. willem.mulder@mssm.edu.
3
Laboratory of Chemical Biology, Department of Biomedical Engineering and Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, Netherlands. willem.mulder@mssm.edu.
4
Department of Medical Biochemistry, Amsterdam University Medical Centers, Academic Medical Center, Amsterdam, Netherlands. willem.mulder@mssm.edu.
5
Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
6
Transplant Immunology Unit, National Centre of Microbiology, Instituto de Salud Carlos III, Madrid, Spain.
7
Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands.
8
Department of Medical Genetics, Iuliu HaĊ£ieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
9
Translational and Molecular Imaging Institute, Department of Radiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
10
Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands. Mihai.Netea@radboudumc.nl.
11
Department for Genomics and Immunoregulation, Life and Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany. Mihai.Netea@radboudumc.nl.

Abstract

Immunotherapy is revolutionizing the treatment of diseases in which dysregulated immune responses have an important role. However, most of the immunotherapy strategies currently being developed engage the adaptive immune system. In the past decade, both myeloid (monocytes, macrophages and dendritic cells) and lymphoid (natural killer cells and innate lymphoid cells) cell populations of the innate immune system have been shown to display long-term changes in their functional programme through metabolic and epigenetic programming. Such reprogramming causes these cells to be either hyperresponsive or hyporesponsive, resulting in a changed immune response to secondary stimuli. This de facto innate immune memory, which has been termed 'trained immunity', provides a powerful 'targeting framework' to regulate the delicate balance of immune homeostasis, priming, training and tolerance. In this Opinion article, we set out our vision of how to target innate immune cells and regulate trained immunity to achieve long-term therapeutic benefits in a range of immune-related diseases. These include conditions characterized by excessive trained immunity, such as inflammatory and autoimmune disorders, allergies and cardiovascular disease and conditions driven by defective trained immunity, such as cancer and certain infections.

PMID:
30967658
DOI:
10.1038/s41573-019-0025-4

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