Indoleamine 2,3-dioxygenase upregulates PD-1 expression on ovarian tumor infiltrating CD8+ T cells via kynurenine activation of the aryl hydrocarbon receptor
Amobi-McCloud, A.; MUTHUSWAMY, R.; Battaglia, S.; Yu, H.; Liu, T.; Wang, J.; Putluri, V.; Singh, P. K.; Qian, F.; Huang, R.-Y.; Putluri, N.; Takemasa, T.; Lugade, A.; Liu, S.; Odunsi, K.
Show abstract
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.
Matching journals
The top 5 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- CXCR6 by increasing retention of memory CD8 T cells in the ovarian tumor microenvironment promotes immunosurveillance and control of ovarian cancer 96%
- Tryptophan depletion sensitizes the AHR pathway by increasing AHR expression and GCN2/LAT1-mediated kynurenine uptake, and potentiates induction of regulatory T lymphocytes 95%
- B cell c-Maf signaling promotes tumor progression in animal models of pancreatic cancer and melanoma 95%
Similar papers in this journal
- ELP-dependent expression of MCL1 promotes resistance to EGFR inhibition in triple-negative breast cancer cells 93%
- Reporter-based screening identifies RAS-RAF stabilizing mutations as drivers of resistance to broad-spectrum RAS inhibition in colorectal cancer 92%
- p16 expression confers sensitivity to CDK2 inhibitors 92%
Similar papers in this journal
- Rapamycin Immunomodulation Utilizes Time-Dependent Alterations of Lymph Node Architecture, Leukocyte Trafficking, and Gut Microbiome 95%
- Tertiary lymphoid structures induced by CXCL13-producing CD4+ T cells increase tumor infiltrating CD8+ T cells and B cells in ovarian cancer 94%
- Enhancing CAR-T Cell Metabolism to Overcome Hypoxic Conditions in the Brain Tumor Microenvironment 94%
Similar papers in this journal
- Cancer immunotherapy by NC410, a LAIR-2 Fc protein blocking LAIR-collagen interaction 95%
- Tumors attenuating the mitochondrial activity in T cells escape from PD-1 blockade therapy 95%
- DECR1 is an androgen-repressed survival factor that regulates PUFA oxidation to protect prostate tumor cells from ferroptosis 95%
Similar papers in this journal
- Activation of the aryl hydrocarbon receptor inhibits neuropilin-1 upregulation on IL-2 responding CD4+ T cells 94%
- Kir6.1, a component of an ATP-sensitive potassium channel, regulates natural killer cell development 94%
- Bcl6 Preserves the Suppressive Function of Regulatory T Cells during Tumorigenesis 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.