Targeting PAR-2 with a negative allosteric modulator increases tumor antigen presentation and potentiates anti-PD-1 immunotherapy
BACKGROUND: expression, encoding the G protein-coupled receptor Protease-Activated Receptor-2 (PAR-2), as a negative biomarker of ICIs responsiveness. This study aims to evaluate the therapeutic potential of targeting PAR-2 to overcome resistance to ICIs. METHODS: dendritic cells. RESULTS: dendritic cells were significantly enhanced following PAR-2 inhibition with I-117. CONCLUSIONS: These findings support PAR-2 inhibition as a strategy to enhance the efficacy of PD-1 blockade, providing a rationale for their combined use in cancer immunotherapy.
Authors
- Lola Lecru (ORCID: https://orcid.org/0000-0002-2780-408X)
- Thibaut Brugat
- Pénélope Desroys du Roure (ORCID: https://orcid.org/0009-0000-0848-5450)
- David Allard (ORCID: https://orcid.org/0000-0001-8820-8161)
- Aurélie Janvier
- John Stagg (ORCID: https://orcid.org/0000-0001-7833-4228)
- Stéphan Schann (ORCID: https://orcid.org/0000-0001-7471-491X)
- Maleck Kadiri
- Camille Fuselier (ORCID: https://orcid.org/0000-0003-3849-3755)
- Christel Franchet
- Antoine Mousson
- Samya Aouad (ORCID: https://orcid.org/0009-0009-1563-8270)
- Anne‐Laure Blayo
- Luc Baron (ORCID: https://orcid.org/0009-0006-2269-3284)
- Julie Malo (ORCID: https://orcid.org/0009-0005-3613-2210)
- Lucie Giraud
- Emma Skora
- Bertrand Routy
Institutions
- McGill University Health Centre (CA)
- Institute for Research in Immunology and Cancer (CA)
- Domain Therapeutics (France) (FR)
- Centre Hospitalier de l’Université de Montréal (CA)
- McGill University (CA)
- Université de Montréal (CA)
Publication Details
- Journal
- Journal for ImmunoTherapy of Cancer
- Published
- 2026-04-01
- DOI
- https://doi.org/10.1136/jitc-2025-013507
- Primary Topic
- Protein Degradation and Inhibitors
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Institute of Cancer Research