Instruct: Identify the main category of Biorxiv papers based on the titles and abstracts
Query: Indoleamine 2,3-dioxygenase upregulates PD-1 expression on ovarian tumor infiltrating CD8+ T cells via kynurenine activation of the aryl hydrocarbon receptor 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.
30
The categories of this paper are: scientific
0
The categories of this paper are: genetics
26
The categories of this paper are: biochemistry
11
The categories of this paper are: cognition
25
The categories of this paper are: bioengineering
28
The categories of this paper are: communication
21
The categories of this paper are: toxicology
31
The categories of this paper are: paleontology
9
The categories of this paper are: synthetic
13
The categories of this paper are: animal
3
The categories of this paper are: evolutionary
22
The categories of this paper are: physiology
24
The categories of this paper are: cancer
20
The categories of this paper are: pharmacology
17
The categories of this paper are: molecular
19
The categories of this paper are: epidemiology