Autocrine Adenosine regulates tumor polyfunctional CD73+CD4+ effector T cells devoid of immune checkpoints
Menée notamment à l'aide d'échantillons sanguins et d'échantillons tumoraux issus de patientes atteintes d'un cancer du sein ou de l'ovaire, cette étude française montre que, dans la tumeur, l'adénosine régule de façon autocrine les cellules T effectrices CD4+ CD73+ dépourvues de point de contrôle immunitaire
The production of CD73-derived Adenosine (Ado) by Tregs, has been proposed as a resistance mechanism to anti-PD1 therapy in murine tumor models. We reported that Human Tregs express the ecto-nucleotidase CD39, that 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 IL-17A/IFN-γ/IL-22/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 IL-17A. 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 non-redundant target for restoring antitumor immunity.
Cancer Research 2018