Year: 2026
Type: article
Abstract: 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 N 6 -threonylcarbamoyladenosine (t 6 A), drives protein homeostasis in cancer cells to maintain T-cell exclusion and prevent anti-tumour immune response. t 6 A-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 t 6 A tRNA modification as a promising therapeutic target for melanoma treatment.
Source: Nature Communications
Authors: 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
Institutions: University of Liège, University of Liverpool, Salford Royal NHS Foundation Trust, University of Manchester, Cancer Research UK Manchester Institute, NIHR Manchester Biomedical Research Centre, Walloon Excellence in Lifesciences and Biotechnology, German Cancer Research Center, Heidelberg University, University Medical Centre Mannheim
Language: English
Topic: RNA modifications and cancer
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Funders: Melanoma Research Alliance, Cancer Research UK, National Institute for Health and Care Research, Department of Health and Social Care, Rosetrees Trust, Fonds De La Recherche Scientifique - FNRS, Fondation contre le Cancer, Walloon excellence in life sciences and biotechnology, Manchester Biomedical Research Centre
OpenAlex ID: W7131370168