Figure S2 from Autocrine Adenosine Regulates Tumor Polyfunctional CD73+CD4+ Effector T Cells Devoid of Immune Checkpoints

Gourdin, Nicolas; Bossennec, Marion; Rodriguez, Céline; Vigano, Selena; Machon, Christelle; Jandus, Camilla; Bauché, David; Faget, Julien; Durand, Isabelle; Chopin, Nicolas; Tredan, Olivier; Marie, Julien C.; Dubois, Bertrand; Guitton, Jérôme; Romero, Pedro; Caux, Christophe; Ménétrier-Caux, Christine

doi:10.1158/0008-5472.22418174.v1

00085472can172405-sup-187599_2_supp_4614446_p59zsb.docx (127.54 kB)

Figure S2 from Autocrine Adenosine Regulates Tumor Polyfunctional CD73⁺CD4⁺ Effector T Cells Devoid of Immune Checkpoints

journal contribution

posted on 2023-03-31, 01:29 authored by Nicolas Gourdin, Marion Bossennec, Céline Rodriguez, Selena Vigano, Christelle Machon, Camilla Jandus, David Bauché, Julien Faget, Isabelle Durand, Nicolas Chopin, Olivier Tredan, Julien C. Marie, Bertrand Dubois, Jérôme Guitton, Pedro Romero, Christophe Caux, Christine Ménétrier-Caux

Impact of rh-ADA on Ado-mediated inhibition of CD73+ or CD73neg CD4+ Teff based on the proliferation marker profiles (Cell Trace Violet or CFSE)

Funding

Breast Cancer Research Foundation

SIRIC project

FP7 European TumAdoR project

LABEX DEVweCAN

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ARTICLE 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.

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Immunology Immunomodulation

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