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

Autor: Aida S. Hansen, Lea S. Jensen, Kristine R. Gammelgaard, Kristoffer G. Ryttersgaard, Christian Krapp, Jesper Just, Kasper L. Jønsson, Pia B. Jensen, Thomas Boesen, Mogens Johannsen, Anders Etzerodt, Bent W. Deleuran, Martin R. Jakobsen
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Journal of Extracellular Vesicles, Vol 12, Iss 8, Pp n/a-n/a (2023)
Druh dokumentu: article
ISSN: 2001-3078
DOI: 10.1002/jev2.12350
Popis: Abstract 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.
Databáze: Directory of Open Access Journals
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