Journal
NATURE REVIEWS DRUG DISCOVERY
Volume 18, Issue 7, Pages 553-566Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41573-019-0025-4
Keywords
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Funding
- National Institutes of Health (NIH) [R01 CA220234, R01 HL144072, P01 HL131478]
- Netherlands Organization for Scientific Research (NWO) grant [ZonMW Vici 91818622]
- NIH [R01 HL143814, P01HL131478]
- Spanish Government [R01 AI 139623, SAF2013-48834-R, SAF2016-80031-R]
- Competitiveness Operational Programme grant of the Romanian Ministry of European Funds (HINT) [P_37_762]
- European Research Council (ERC) Consolidator Grant [310372]
- NWO Spinoza Prize
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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.
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