T-cell derived extracellular vesicles prime macrophages for improved STING based cancer immunotherapy.

Autor: Hansen AS; Department of Biomedicine, Aarhus University, Health, Aarhus Midtjylland, Denmark., Jensen LS; Department of Biomedicine, Aarhus University, Health, Aarhus Midtjylland, Denmark., Gammelgaard KR; Department of Biomedicine, Aarhus University, Health, Aarhus Midtjylland, Denmark., Ryttersgaard KG; Department of Biomedicine, Aarhus University, Health, Aarhus Midtjylland, Denmark., Krapp C; Department of Biomedicine, Aarhus University, Health, Aarhus Midtjylland, Denmark., Just J; Department of Clinical Medicine, Center of Functionally Integrative Neuroscience, Aarhus University, Aarhus Midtjylland, Denmark., Jønsson KL; Department of Biomedicine, Aarhus University, Health, Aarhus Midtjylland, Denmark., Jensen PB; Interdiciplinary Nanoscience Center - iNANO, Aarhus University, Aarhus Midtjylland, Denmark., Boesen T; Interdiciplinary Nanoscience Center - iNANO, Aarhus University, Aarhus Midtjylland, Denmark., Johansen M; Department of Forensic Medicine, Aarhus University, Aarhus Midtjylland, Denmark., Etzerodt A; Department of Biomedicine, Aarhus University, Health, Aarhus Midtjylland, Denmark., Deleuran BW; Department of Biomedicine, Aarhus University, Health, Aarhus Midtjylland, Denmark., Jakobsen MR; Department of Biomedicine, Aarhus University, Health, Aarhus Midtjylland, Denmark.
Jazyk: angličtina
Zdroj: Journal of extracellular vesicles [J Extracell Vesicles] 2023 Aug; Vol. 12 (8), pp. e12350.
DOI: 10.1002/jev2.12350
Abstrakt: A key phenomenon in cancer is the establishment of a highly immunosuppressive tumour microenvironment (TME). Despite advances in immunotherapy, where the purpose is to induce tumour recognition and hence hereof tumour eradication, the majority of patients applicable for such treatment still fail to respond. It has been suggested that high immunological activity in the tumour is essential for achieving effective response to immunotherapy, which therefore have led to exploration of strategies that triggers inflammatory pathways. Here activation of the stimulator of interferon genes (STING) signalling pathway has been considered an attractive target, as it is a potent trigger of pro-inflammatory cytokines and types I and III interferons. However, immunotherapy combined with targeted STING agonists has not yielded sustained clinical remission in humans. This suggests a need for exploring novel adjuvants to improve the innate immunological efficacy. Here, we demonstrate that extracellular vesicles (EVs), derived from activated CD4 + T cells (T-EVs), sensitizes macrophages to elevate STING activation, mediated by IFNγ carried on the T-EVs. Our work support that T-EVs can disrupt the immune suppressive environment in the tumour by reprogramming macrophages to a pro-inflammatory phenotype, and priming them for a robust immune response towards STING activation.
(© 2023 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles.)
Databáze: MEDLINE
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