Exploring the role of readthrough-inducing molecule 2,6-diaminopurine to increase immune response against cancer cells
Immuno-oncotherapy is a highly promising therapeutic strategy that relies on the ability of cancer cells to present specific antigenic epitopes at their surfaces. Because they proliferate rapidly, cancer cells frequently accumulate genetic variants, including premature termination codons. In this study, we investigated the potential of 2,6-diaminopurine (DAP), a potent translational-readthrough-inducing molecule, to elicit an antitumor immune response. Readthrough-resulting proteins following DAP treatment can be displayed at the cell surface by the major histocompatibility complex, thus potentially enhancing immune recognition. This was demonstrated using a construct encoding FIREFLY LUCIFERASE interrupted by a UGA stop codon and fused at its C terminus with the SL8 antigenic peptide. Furthermore, in vivo exposure to DAP promotes the recruitment of immune effector cells, including T lymphocytes, macrophages, and natural killer cells, to the tumor microenvironment. These findings suggest that DAP and potentially other translational readthrough-inducing molecules hold promise as novel candidate drugs for antitumor therapy.
Authors
- Fabrice Lejeune (ORCID: https://orcid.org/0000-0002-5132-3585)
- Philippe Froguel (ORCID: https://orcid.org/0000-0003-2972-0784)
- Isabelle Van Seuningen (ORCID: https://orcid.org/0000-0002-3131-2694)
- Tristan Cardon (ORCID: https://orcid.org/0000-0003-1751-0528)
- Charles Pineau (ORCID: https://orcid.org/0000-0002-7461-5433)
- Emmanuelle Com (ORCID: https://orcid.org/0000-0002-7401-817X)
- Amélie Bonnefond (ORCID: https://orcid.org/0000-0001-9976-3005)
- Nicolas Jonckheere (ORCID: https://orcid.org/0000-0002-0496-0661)
- Michel Salzet (ORCID: https://orcid.org/0000-0003-4318-0817)
- Catherine Leroy
- Fabrice Soncin (ORCID: https://orcid.org/0000-0001-6312-0673)
- Thierry Chassat
- Rob Lavigne (ORCID: https://orcid.org/0000-0001-7377-1314)
- Roland P. Bourette (ORCID: https://orcid.org/0000-0003-2074-4878)
- Nathalie Jouy (ORCID: https://orcid.org/0009-0001-4598-6518)
- Blandine Guével (ORCID: https://orcid.org/0000-0002-4592-603X)
- Bénédicte Toussaint
- Daniela Barros (ORCID: https://orcid.org/0000-0002-7104-0267)
- Bélinda Duchêne (ORCID: https://orcid.org/0000-0002-4810-4680)
- Philippe Pierre (ORCID: https://orcid.org/0000-0003-0863-8255)
- Mehdi Derhourhi (ORCID: https://orcid.org/0000-0001-5020-5379)
- Alice M. Leroy
- Julie Carrard
- Carmen Sandoval Pacheco
Institutions
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Université de Lille (FR)
- Institut Pasteur de Lille (FR)
- Centre Hospitalier Universitaire de Lille (FR)
- Centre de Recherche Jean Pierre Aubert (FR)
- Institut de Recherche en Santé, Environnement et Travail (FR)
- Institut de Biologie de Lille (FR)
- Protéomique, Réponse Inflammatoire et Spectrométrie de Masse (FR)
- Université de Rennes (FR)
- University of Aveiro (PT)
- The University of Tokyo (JP)
Publication Details
- Journal
- Molecular Therapy
- Published
- 2025-09-13
- DOI
- https://doi.org/10.1016/j.ymthe.2025.09.024
- Citations
- 1
- Primary Topic
- Synthesis and Biological Evaluation
- Type
- article
- Field-Weighted Citation Impact
- 0.94
Funders
- Infrastructures en Biologie Santé et Agronomie
- Université de Lille
- European Commission
- Agence Nationale de la Recherche
- Institut National de la Santé et de la Recherche Médicale
- Ligue Contre le Cancer
- Centre National de la Recherche Scientifique
- Institut National Du Cancer
- Région Hauts-de-France
- Conseil Régional Hauts-de-France
- European Regional Development Fund
- CHIST-ERA