Autocrine Adenosine Regulates Tumor Polyfunctional CD73 + CD4 + Effector T Cells Devoid of Immune Checkpoints.

Autor:	Gourdin N; Univ Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS, Centre Léon Bérard, Cancer Research Center of Lyon, Lyon, France.; Team 11, Immunology Virology Inflammation (IVI) Department, INSERM U-1052, Cancer Research Center of Lyon, Lyon, France.; Innovation and Translational Research Department, Centre Léon Bérard, Lyon, France., Bossennec M; Univ Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS, Centre Léon Bérard, Cancer Research Center of Lyon, Lyon, France.; Team 11, Immunology Virology Inflammation (IVI) Department, INSERM U-1052, Cancer Research Center of Lyon, Lyon, France., Rodriguez C; Univ Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS, Centre Léon Bérard, Cancer Research Center of Lyon, Lyon, France.; Team 11, Immunology Virology Inflammation (IVI) Department, INSERM U-1052, Cancer Research Center of Lyon, Lyon, France.; Innovation and Translational Research Department, Centre Léon Bérard, Lyon, France., Vigano S; Ludwig Cancer Research Center, Department of Oncology, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland., Machon C; Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Laboratoire de Biochimie et Toxicologie, Pierre-Bénite, France.; Université de Lyon, Université Lyon 1, ISPB Faculté de pharmacie, Laboratoire de Chimie Analytique, Lyon, France., Jandus C; Ludwig Cancer Research Center, Department of Oncology, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland., Bauché D; Team 11, Immunology Virology Inflammation (IVI) Department, INSERM U-1052, Cancer Research Center of Lyon, Lyon, France.; TGF-β and Immuno-evasion Department of Immunology Virology and Inflammation, INSERM U1052, Cancer Research Center of Lyon, Lyon, France.; TGF-β and Immuno-evasion, Tumor immunology Program, DKFZ, Heidelberg, Germany., Faget J; Univ Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS, Centre Léon Bérard, Cancer Research Center of Lyon, Lyon, France.; Team 11, Immunology Virology Inflammation (IVI) Department, INSERM U-1052, Cancer Research Center of Lyon, Lyon, France.; Innovation and Translational Research Department, Centre Léon Bérard, Lyon, France., Durand I; Team 11, Immunology Virology Inflammation (IVI) Department, INSERM U-1052, Cancer Research Center of Lyon, Lyon, France.; Cytometry platform, INSERM U-1052, Cancer Research Center of Lyon, Lyon, France., Chopin N; Centre Léon Bérard, Medical Oncology Department, Lyon, France., Tredan O; Centre Léon Bérard, Medical Oncology Department, Lyon, France., Marie JC; Team 11, Immunology Virology Inflammation (IVI) Department, INSERM U-1052, Cancer Research Center of Lyon, Lyon, France.; TGF-β and Immuno-evasion Department of Immunology Virology and Inflammation, INSERM U1052, Cancer Research Center of Lyon, Lyon, France.; TGF-β and Immuno-evasion, Tumor immunology Program, DKFZ, Heidelberg, Germany., Dubois B; Univ Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS, Centre Léon Bérard, Cancer Research Center of Lyon, Lyon, France.; Team 11, Immunology Virology Inflammation (IVI) Department, INSERM U-1052, Cancer Research Center of Lyon, Lyon, France., Guitton J; Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Laboratoire de Biochimie et Toxicologie, Pierre-Bénite, France.; Université de Lyon, Université Lyon 1, ISPB Faculté de pharmacie, Laboratoire de Toxicologie, Lyon, France., Romero P; Ludwig Cancer Research Center, Department of Oncology, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland., Caux C; Univ Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS, Centre Léon Bérard, Cancer Research Center of Lyon, Lyon, France.; Team 11, Immunology Virology Inflammation (IVI) Department, INSERM U-1052, Cancer Research Center of Lyon, Lyon, France.; Innovation and Translational Research Department, Centre Léon Bérard, Lyon, France., Ménétrier-Caux C; Univ Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS, Centre Léon Bérard, Cancer Research Center of Lyon, Lyon, France. christine.caux@lyon.unicancer.fr.; Team 11, Immunology Virology Inflammation (IVI) Department, INSERM U-1052, Cancer Research Center of Lyon, Lyon, France.; Innovation and Translational Research Department, Centre Léon Bérard, Lyon, France.
Jazyk:	angličtina
Zdroj:	Cancer research [Cancer Res] 2018 Jul 01; Vol. 78 (13), pp. 3604-3618. Date of Electronic Publication: 2018 Mar 20.
DOI:	10.1158/0008-5472.CAN-17-2405
Abstrakt:	The production of CD73-derived adenosine (Ado) by Tregs has been proposed as a resistance mechanism to anti-PD-1 therapy in murine tumor models. We reported that human Tregs express the ectonucleotidase CD39, which generates AMP from ATP, but do not express the AMPase CD73. In contrast, CD73 defined a subset of effector CD4 + T cells (Teffs) enriched in polyfunctional Th1.17 cells characterized by expression of CXCR3, CCR6, and MDR1, and production of IL17A/IFNγ/IL22/GM-CSF. CD39 + Tregs selectively targeted CD73 + Teffs through cooperative degradation of ATP into Ado inhibiting and restricting the ability of CD73 + Teffs to secrete IL17A. CD73 + Teffs infiltrating breast and ovarian tumors were functionally blunted by Tregs expressing upregulated levels of CD39 and ATPase activity. Moreover, tumor-infiltrating CD73 + Teffs failed to express inhibitory immune checkpoints, suggesting that CD73 might be selected under pressure from immune checkpoint blockade therapy and thus may represent a nonredundant target for restoring antitumor immunity. Significance: Polyfunctional CD73 + T-cell effectors lacking other immune checkpoints are selectively targeted by CD39 overexpressing Tregs that dominate the breast tumor environment. Cancer Res; 78(13); 3604-18. ©2018 AACR . (©2018 American Association for Cancer Research.)
Databáze:	MEDLINE
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