| First Author | Amobi-McCloud A | Year | 2021 |
| Journal | Front Immunol | Volume | 12 |
| Pages | 678999 | PubMed ID | 34025677 |
| Mgi Jnum | J:341829 | Mgi Id | MGI:6741817 |
| Doi | 10.3389/fimmu.2021.678999 | Citation | Amobi-McCloud A, et al. (2021) IDO1 Expression in Ovarian Cancer Induces PD-1 in T Cells via Aryl Hydrocarbon Receptor Activation. Front Immunol 12:678999 |
| abstractText | The immunoregulatory enzyme, indoleamine 2,3-dioxygenase (IDO1) and the PD-1/PD-L1 axis are potent mechanisms that impede effective anti-tumor immunity in ovarian cancer. However, whether the IDO pathway regulates PD-1 expression in T cells is currently unknown. Here we show that tumoral IDO1 expression led to profound changes in tryptophan, nicotinate/nicotinamide, and purine metabolic pathways in the ovarian tumor microenvironment, and to an increased frequency of PD-1(+)CD8(+) tumor infiltrating T cells. We determined that activation of the aryl hydrocarbon receptor (AHR) by kynurenine induced PD-1 expression, and this effect was significantly abrogated by the AHR antagonist CH223191. Mechanistically, kynurenine alters chromatin accessibility in regulatory regions of T cell inhibitory receptors, allowing AHR to bind to consensus XRE motifs in the promoter region of PD-1. These results enable the design of strategies to target the IDO1 and AHR pathways for enhancing anti-tumor immunity in ovarian cancer. |
