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Journal articles
Inhibition of the dipeptidyl peptidase DPP4 (CD26) reveals IL-33-dependent eosinophil-mediated control of tumor growth
Clémence Hollande
1
Jeremy Boussier
1
James Ziai
2
Tamaki Nozawa
2
Vincent Bondet
1
Wilson Phung
2
Binfeng Lu
3
Darragh Duffy
1, 4
Valérie Paradis
5
Vincent Mallet
6
Gerard Eberl
7
Wendy Sandoval
2
Jill Schartner
2
Stanislas Pol
1, 4
Rosa Barreira da Silva
2
Matthew Albert
2, *
*
Corresponding author
Jill Schartner 2
Author
Stanislas Pol 1, 4
Author
Rosa Barreira da Silva 2
Author
Matthew Albert 2
Correspondent author
1
Immunobiologie des Cellules dendritiques (Département d'Immunologie, 25-28 rue du Docteur Roux, 75724 Paris cedex 15 - )
- Institut Pasteur [Paris] (25-28, rue du docteur Roux, 75724 Paris cedex 15 - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U1223 (101, rue de Tolbiac, 75013 Paris - France)
2
Genentech, Inc. [San Francisco] (San Francisco - United States)
3
PITT - University of Pittsburgh (4200 Fifth Avenue Pittsburgh, PA 15260 - United States)
- Pennsylvania Commonwealth System of Higher Education (PCSHE) (United States)
4
CRT - Centre de Recherche Translationnelle (25-28 rue du docteur Roux, 75724 Paris cedex 15
- France)
- Institut Pasteur [Paris] (25-28, rue du docteur Roux, 75724 Paris cedex 15 - France)
5
Service d’Anatomie Pathologique [CHU Beaujon] (France)
- AP-HP - Assistance publique - Hôpitaux de Paris (AP-HP) (France)
- Hôpital Beaujon [AP-HP] (100, boulevard du Général Leclerc 92 Clichy - France)
6
Service d'hépatologie médicale [CHU Cochin] (27, rue du Faubourg Saint-Jacques 75014 Paris - France)
- AP-HP - Assistance publique - Hôpitaux de Paris (AP-HP) (France)
- CHU Cochin [AP-HP] (27 Rue du Faubourg Saint-Jacques 75014 Paris - France)
7
Microenvironnement et Immunité (Département d'Immunologie, 25-28 rue du docteur Roux, 75724 Paris Cedex 15 - France)
- Institut Pasteur [Paris] (25-28, rue du docteur Roux, 75724 Paris cedex 15 - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U1224 (101, rue de Tolbiac, 75013 Paris - France)
Abstract : Post-translational modification of chemokines mediated by the dipeptidyl peptidase DPP4 (CD26) has been shown to negatively regulate lymphocyte trafficking, and its inhibition enhances T cell migration and tumor immunity by preserving functional chemokine CXCL10. By extending those initial findings to pre-clinical models of hepatocellular carcinoma and breast cancer, we discovered a distinct mechanism by which inhibition of DPP4 improves anti-tumor responses. Administration of the DPP4 inhibitor sitagliptin resulted in higher concentrations of the chemokine CCL11 and increased migration of eosinophils into solid tumors. Enhanced tumor control was preserved in mice lacking lymphocytes and was ablated after depletion of eosinophils or treatment with degranulation inhibitors. We further demonstrated that tumor-cell expression of the alarmin IL-33 was necessary and sufficient for eosinophil-mediated anti-tumor responses and that this mechanism contributed to the efficacy of checkpoint-inhibitor therapy. These findings provide insight into IL-33- and eosinophil-mediated tumor control, revealed when endogenous mechanisms of DPP4 immunoregulation are inhibited.
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Journal articles
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https://hal-pasteur.archives-ouvertes.fr/pasteur-02063831
Contributor : Marie-Christine Vougny <>
Submitted on : Monday, March 11, 2019 - 3:04:47 PM
Last modification on : Monday, December 14, 2020 - 3:40:34 PM
Contributor : Marie-Christine Vougny <>
Submitted on : Monday, March 11, 2019 - 3:04:47 PM
Last modification on : Monday, December 14, 2020 - 3:40:34 PM
Identifiers
- HAL Id : pasteur-02063831, version 1
- DOI : 10.1038/s41590-019-0321-5
- PUBMED : 30778250
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Citation
Clémence Hollande, Jeremy Boussier, James Ziai, Tamaki Nozawa, Vincent Bondet, et al.. Inhibition of the dipeptidyl peptidase DPP4 (CD26) reveals IL-33-dependent eosinophil-mediated control of tumor growth. Nature Immunology, Nature Publishing Group, 2019, 20 (3), pp.257-264. ⟨10.1038/s41590-019-0321-5⟩. ⟨pasteur-02063831⟩
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