Therapeutic targeting of trained immunity
Willem J. M. Mulder,Jordi Ochando,Jordi Ochando,Leo A. B. Joosten,Leo A. B. Joosten,Zahi A. Fayad,Mihai G. Netea,Mihai G. Netea +7 more
TLDR
The mechanisms responsible for the induction of trained immunity are described and strategies to regulate it are proposed as a potential treatment of immune-related diseases.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.read more
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Defining trained immunity and its role in health and disease
Mihai G. Netea,Mihai G. Netea,Jorge Domínguez-Andrés,Luis B. Barreiro,Luis B. Barreiro,Triantafyllos Chavakis,Triantafyllos Chavakis,Maziar Divangahi,Maziar Divangahi,Elaine Fuchs,Leo A. B. Joosten,Jos W. M. van der Meer,Musa M. Mhlanga,Musa M. Mhlanga,Willem J. M. Mulder,Willem J. M. Mulder,Niels P. Riksen,Andreas Schlitzer,Joachim L. Schultze,Christine Stabell Benn,Joseph C. Sun,Joseph C. Sun,Ramnik J. Xavier,Ramnik J. Xavier,Eicke Latz,Eicke Latz,Eicke Latz +26 more
TL;DR: A group of leaders in the field define ‘trained immunity’ as a biological process and discuss the innate stimuli and the epigenetic and metabolic reprogramming events that shape the induction of trained immunity.
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Smart cancer nanomedicine
Roy van der Meel,Einar Sulheim,Einar Sulheim,Yang Shi,Fabian Kiessling,Willem J. M. Mulder,Willem J. M. Mulder,Twan Lammers,Twan Lammers,Twan Lammers +9 more
TL;DR: The use of nanomedicine in cancer requires the adoption of specific strategies to optimize its potential, and this perspective proposes four strategies including the identification of patients for clinical trials, investments in modular nanocarrier design, the integration in multimodal combination therapy regimes and the inclusion in immunotherapy studies.
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Enhancing cancer immunotherapy with nanomedicine.
Darrell J. Irvine,Eric L. Dane +1 more
TL;DR: How nanomedicine-based treatment strategies are well suited to immunotherapy on the basis of nanomaterials’ ability to direct immunomodulators to tumours and lymphoid organs, to alter the way biologics engage with target immune cells and to accumulate in myeloid cells in tumour and systemic compartments is discussed.
Poster: Hyperglycemia induces a dynamic cooperativity of histone methylase and demethylase enzymes associated with gene-activating epigenetic marks that coexist on the lysine tail
Assam El-Osta,Assam El-Osta +1 more
TL;DR: In this article, transient hyperglycemia was used to link NFκB-p65 gene expression with H3K4 modifications mediated by the histone methyltransferases (Set7 and SuV39h1) and the lysine-specific demethylase (LSD1).
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Emerging concepts in the science of vaccine adjuvants.
TL;DR: A review of the known knowns and known unknowns of adjuvants can be found in this article, where the authors discuss emerging concepts and highlight how our expanding knowledge about innate immunity and systems vaccinology are revitalizing the science and development of novel adjuants for use in vaccines against COVID-19 and future pandemics.
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