| Added by | Nathalie Bonnefoy |
|---|---|
| Group name | EquipeNB |
| Item Type | Journal Article |
| Title | Autocrine Adenosine Regulates Tumor Polyfunctional CD73+CD4+ Effector T Cells Devoid of Immune Checkpoints |
| Creator | Gourdin et al. |
| Author | Nicolas Gourdin |
| Author | Marion Bossennec |
| Author | Céline Rodriguez |
| Author | Selena Vigano |
| Author | Christelle Machon |
| Author | Camilla Jandus |
| Author | David Bauché |
| Author | Julien Faget |
| Author | Isabelle Durand |
| Author | Nicolas Chopin |
| Author | Olivier Tredan |
| Author | Julien C. Marie |
| Author | Bertrand Dubois |
| Author | Jérôme Guitton |
| Author | Pedro Romero |
| Author | Christophe Caux |
| Author | Christine Ménétrier-Caux |
| 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/IFN?/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. |
| Publication | Cancer Research |
| Volume | 78 |
| Issue | 13 |
| Pages | 3604-3618 |
| Date | Jul 01, 2018 |
| Journal Abbr | Cancer Res. |
| Language | eng |
| DOI | 10.1158/0008-5472.CAN-17-2405 |
| ISSN | 1538-7445 |
| Library Catalog | PubMed |
| Extra | PMID: 29559470 |
| Tags | original |
| Date Added | 2019/05/28 - 21:13:58 |
| Date Modified | 2019/05/28 - 21:14:15 |
| Notes and Attachments | PubMed entry (Attachment) Texte intégral (Attachment) |
Institut de Recherche en Cancérologie de
