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Disruption of tRNA threonylation triggers RIG-I mediated anti-tumour immune response

Tumour-induced mechanisms of immune evasion hinder immune response to cancer, particularly in melanoma. mRNA translation, by ensuring accurate protein synthesis, regulates cancer phenotypes and immune response, but the underlying mechanisms remain unclear. Here, we reveal how O-sialoglycoprotein end...

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Main Authors: Dziagwa, Cléa (Author) , Seca, Christian (Author) , Capron, Coralie (Author) , Maurizy, Chloe (Author) , An, Ning (Author) , Heusdens, Denis (Author) , Budden, Timothy (Author) , Martin-Morales, Lorena (Author) , Susaeta Ruiz, Miguel (Author) , Renaude, Elodie (Author) , El-Hachem, Najla (Author) , Vanleyssem, Raphael (Author) , Leclercq, Marine (Author) , Blomme, Arnaud (Author) , Chariot, Alain (Author) , Utikal, Jochen (Author) , Viros, Amaya (Author) , Rapino, Francesca (Author) , Delaunay, Sylvain (Author) , Close, Pierre (Author)
Format: Article (Journal)
Language:English
Published: 25 February 2026
In: Nature Communications
Year: 2026, Volume: 17, Pages: 1-18
ISSN:2041-1723
DOI:10.1038/s41467-026-69964-2
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s41467-026-69964-2
Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s41467-026-69964-2
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Author Notes:Cléa Dziagwa, Christian Seca, Coralie Capron, Chloe Maurizy, Ning An, Denis Heusdens, Timothy Budden, Lorena Martin-Morales, Miguel Susaeta Ruiz, Elodie Renaude, Najla El-Hachem, Raphael Vanleyssem, Marine Leclercq, Arnaud Blomme, Alain Chariot, Jochen Utikal, Amaya Viros, Francesca Rapino, Sylvain Delaunay & Pierre Close
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Summary:Tumour-induced mechanisms of immune evasion hinder immune response to cancer, particularly in melanoma. mRNA translation, by ensuring accurate protein synthesis, regulates cancer phenotypes and immune response, but the underlying mechanisms remain unclear. Here, we reveal how O-sialoglycoprotein endopeptidase (OSGEP), catalysing the tRNA modification N6-threonylcarbamoyladenosine (t6A), drives protein homeostasis in cancer cells to maintain T-cell exclusion and prevent anti-tumour immune response. t6A-deficient melanoma cells disrupt efficient cytoplasmic translation of ANN codons (trinucleotides with A in the first position and N = any nucleotide), causing specific protein aggregation and the formation of integrated stress response-dependent stress granules. We discovered that OSGEP loss triggers melanoma regression by relocating RIG-I to stress granules, leading to its pathway activation. As a result, T-cells are recruited to the tumour site and orchestrate an anti-tumour immune response. Finally, an OSGEP-driven gene signature in melanoma patients is associated with T-cell infiltration and improved overall survival. Together, our findings position t6A tRNA modification as a promising therapeutic target for melanoma treatment.
Item Description:Gesehen am 20.04.2026
Physical Description:Online Resource
ISSN:2041-1723
DOI:10.1038/s41467-026-69964-2

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