Epigenetic Regulation of Ovarian Tumor Immunity

2010 ◽  
Author(s):  
Protul A. Shrikant
Keyword(s):  
Tumor Immunity ◽  
Epigenetic Regulation ◽  
Ovarian Tumor

Abstract NTOC-100: OVARIAN TUMOR-ASSOCIATED GRP78 INDUCES IMMUNOSUPPRESSION AND WITHAFERIN A (ASHWAGANDHA) ENHANCES ANTI-TUMOR IMMUNITY

2017 ◽  
Author(s):  
Sa'Rah McNeal ◽  
Pincas Bitterman ◽  
Janice M Bahr ◽  
William P Hanafin ◽  
Sameer Sharma ◽  
...  
Keyword(s):  
Tumor Immunity ◽  
Ovarian Tumor ◽  
Withaferin A

scholarly journals Indoleamine 2,3-dioxygenase upregulates PD-1 expression on ovarian tumor infiltrating CD8+ T cells via kynurenine activation of the aryl hydrocarbon receptor

2021 ◽  
Author(s):  
Adaobi Amobi-McCloud ◽  
Ravikumar Muthuswamy ◽  
Sebastiano Battaglia ◽  
Han Yu ◽  
Tao Liu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
T Cells ◽  
Aryl Hydrocarbon Receptor ◽  
Tumor Immunity ◽  
Metabolic Pathways ◽  
Ovarian Tumor ◽  
Chromatin Accessibility ◽  
Indoleamine 2,3 Dioxygenase ◽  
Aryl Hydrocarbon ◽  
Ido1 Expression

AbstractThe 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.

scholarly journals IDO1 Expression in Ovarian Cancer Induces PD-1 in T Cells via Aryl Hydrocarbon Receptor Activation

2021 ◽  
Vol 12 ◽  
Author(s):  
Adaobi Amobi-McCloud ◽  
Ravikumar Muthuswamy ◽  
Sebastiano Battaglia ◽  
Han Yu ◽  
Tao Liu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
T Cells ◽  
Aryl Hydrocarbon Receptor ◽  
Tumor Immunity ◽  
Metabolic Pathways ◽  
Ovarian Tumor ◽  
Receptor Activation ◽  
Chromatin Accessibility ◽  
Aryl Hydrocarbon ◽  
Ido1 Expression

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.

scholarly journals Epigenetic regulation of cancer biology and anti-tumor immunity by EZH2

Oncotarget ◽  
2016 ◽  
Vol 7 (51) ◽  
pp. 85624-85640 ◽  
Author(s):  
Anthos Christofides ◽  
Theodoros Karantanos ◽  
Kankana Bardhan ◽  
Vassiliki A. Boussiotis
Keyword(s):  
Tumor Immunity ◽  
Epigenetic Regulation ◽  
Cancer Biology

Prognostic relevance of disordered epigenetic regulation in juvenile myelomonocytic leukemia

2013 ◽  
Vol 225 (03) ◽  
Author(s):  
S Fluhr ◽  
T Witte ◽  
CF Krombholz ◽  
C Plass ◽  
CM Niemeyer ◽  
...  
Keyword(s):  
Epigenetic Regulation ◽  
Juvenile Myelomonocytic Leukemia ◽  
Prognostic Relevance ◽  
Myelomonocytic Leukemia

Epigenetic regulation of hepatic DPP4

2017 ◽  
Vol 12 (S 01) ◽  
pp. S1-S84
Author(s):  
S Saussenthaler ◽  
C Baumeier ◽  
A Kammel ◽  
M Canouil ◽  
S Lobbens ◽  
...  
Keyword(s):  
Epigenetic Regulation
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