Abstract：
: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.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Gourdin N,Bossennec M,Rodriguez C,Vigano S,Machon C,Jandus C,Bauché D,Faget J,Durand I,Chopin N,Tredan O,Marie JC,Dubois B,Guitton J,Romero P,Caux C,Ménétrier-Caux Cdoi
10.1158/0008-5472.CAN-17-2405subject
Has Abstractpub_date
2018-07-01 00:00:00pages
3604-3618issue
13eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-17-2405journal_volume
78pub_type
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