Dipeptidylpeptidase 4 inhibition enhances lymphocyte trafficking, improving both naturally occurring tumor immunity and immunotherapy
| Autor: | Rosa Barreira da Silva, Melissa E Laird, Nader Yatim, Laurence Fiette, Molly A Ingersoll, Matthew L Albert |
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| Přispěvatelé: | Immunobiologie des Cellules Dendritiques, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Histopathologie humaine et Modèles animaux, Institut Pasteur [Paris] (IP), Funding was provided by the Institut Pasteur (Pasteur-Roux post-doctoral fellowship to R.B.d.S.), the Pasteur Foundation (fellowship to M.E.L.), the Ligue Contre le Cancer (M.L.A.), the Fondation ARC pour la recherche sur le cancer (M.L.A.) and the French government's Invest in the Future Program, managed by the Agence Nationale de la Recherche (LabEx Immuno-Onco (R.B.d.S., M.E.L., N.Y., M.A.I. and M.L.A.))., ANR-11-IDEX-0005,USPC,Université Sorbonne Paris Cité(2011), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Male
Adoptive cell transfer Lymphocyte medicine.medical_treatment Cancer immunotherapy MESH: Flow Cytometry CXCR3 MESH: Mice Knockout MESH: Cell Movement/drug effects 0302 clinical medicine Cell Movement MESH: Triazoles/pharmacology Immunology and Allergy MESH: Animals MESH: Chemokines/metabolism Lymphocytes Mice Knockout Mice Inbred BALB C 0303 health sciences Chemistry Flow Cytometry Adoptive Transfer 3. Good health MESH: Dipeptidyl Peptidase 4/immunology medicine.anatomical_structure MESH: Neoplasms Experimental/genetics MESH: Dipeptidyl Peptidase 4/genetics MESH: Pyrazines/pharmacology Pyrazines 030220 oncology & carcinogenesis MESH: Neoplasms Experimental/immunology MESH: Chemokine CXCL10/metabolism [SDV.IMM]Life Sciences [q-bio]/Immunology Female Immunotherapy Chemokines MESH: Chemokine CXCL10/immunology Receptors CXCR3 MESH: Cell Line Tumor MESH: Mice Transgenic Dipeptidyl Peptidase 4 T cell Immunology MESH: Mice Inbred BALB C MESH: Immunotherapy/methods MESH: Cell Movement/immunology Mice Transgenic MESH: Receptors CXCR3/immunology 03 medical and health sciences Immune system MESH: Mice Inbred C57BL Cell Line Tumor MESH: Lymphocytes/metabolism medicine Animals CXCL10 MESH: Sitagliptin Phosphate 030304 developmental biology MESH: Neoplasms Experimental/therapy Dipeptidyl-Peptidase IV Inhibitors Protein transport MESH: Dipeptidyl-Peptidase IV Inhibitors/pharmacology Sitagliptin Phosphate Neoplasms Experimental Triazoles MESH: Male Chemokine CXCL10 Mice Inbred C57BL MESH: Adoptive Transfer MESH: Receptors CXCR3/metabolism MESH: Dipeptidyl Peptidase 4/metabolism MESH: Lymphocytes/immunology MESH: Female MESH: Chemokines/immunology |
| Zdroj: | Nature Immunology Nature Immunology, 2015, 16 (8), pp.850-858. ⟨10.1038/ni.3201⟩ Nature Immunology, Nature Publishing Group, 2015, 16 (8), pp.850-858. ⟨10.1038/ni.3201⟩ |
| ISSN: | 1529-2908 1529-2916 |
| DOI: | 10.1038/ni.3201⟩ |
| Popis: | International audience; The success of antitumor immune responses depends on the infiltration of solid tumors by effector T cells, a process guided by chemokines. Here we show that in vivo post-translational processing of chemokines by dipeptidylpeptidase 4 (DPP4, also known as CD26) limits lymphocyte migration to sites of inflammation and tumors. Inhibition of DPP4 enzymatic activity enhanced tumor rejection by preserving biologically active CXCL10 and increasing trafficking into the tumor by lymphocytes expressing the counter-receptor CXCR3. Furthermore, DPP4 inhibition improved adjuvant-based immunotherapy, adoptive T cell transfer and checkpoint blockade. These findings provide direct in vivo evidence for control of lymphocyte trafficking via CXCL10 cleavage and support the use of DPP4 inhibitors for stabilizing biologically active forms of chemokines as a strategy to enhance tumor immunotherapy. |
| Databáze: | OpenAIRE |
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