Indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors in clinical trials for cancer immunotherapy

Tang, Kai; Wu, Yahong; Song, Yihui; Yu, Bin

doi:10.1186/s13045-021-01080-8

Cited by 230 publications

(142 citation statements)

References 97 publications

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“…Jason Luke mentions that this treatment reduced the serum levels of kynurenine and induced an increase in the number of cytotoxic T cells in most of the patients. Analysis of the effect of this immunotherapy on NK cells has yet to be conducted [77][78][79]. Another enzyme involved in the evasion of the response of NK cells, and that is expressed in cervical tumour cells, is haem oxygenase 1 (HO-1).…”

Section: Treatments That Enhance Nk Cell Activitymentioning

confidence: 99%

NK Cell Regulation in Cervical Cancer and Strategies for Immunotherapy

Gutiérrez‐Hoya

Soto‐Cruz²

2021

Cells

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Cervical cancer is one of the most prevalent gynaecological malignancies worldwide and is related to human papillomavirus (HPV) infection, viral persistence, progression, and invasion. Therefore, the immune response is linked to HPV status. Natural killer (NK) cells play a central role against virus-infected cells and tumours through a delicate balance between activating and inhibitory receptors and secretion of cytokines and chemokines. These cells also play a crucial role in tumour immunosurveillance. For these reasons, there is growing interest in harnessing NK cells as an immunotherapy for cervical cancer. These studies are diverse and include many strategies such as transferring activated autologous or allogeneic NK cells, improving the activation and cytolytic activity of NK cells using cytokines or analogues and modifying chimeric antigen receptors to increase specificity and targeting NK cells. However, research regarding the application of NK cells in immunotherapy is limited. This article focuses on recent discoveries about using NK cells to prevent and treat cervical cancer and the possibility of cellular immunotherapy becoming one of the best strategies to exploit the immune system to fight tumours.

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Section: Treatments That Enhance Nk Cell Activitymentioning

confidence: 99%

NK Cell Regulation in Cervical Cancer and Strategies for Immunotherapy

Gutiérrez‐Hoya

Soto‐Cruz²

2021

Cells

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“…However, since the role of IDO on I-R injury-induced renal senescence has never been evaluated before, our study could be considered a starting point. Interestingly, IDO inhibitors have already been tested in clinical trials on cancer immunotherapy, and much is known about their pharmacokinetics and safety [39]. In addition, as already noted, I-R injury consists of two consecutive but pathophysiologically distinct phases.…”

Section: Discussionmentioning

confidence: 98%

The Role of Indoleamine 2,3-Dioxygenase in Renal Tubular Epithelial Cells Senescence under Anoxia or Reoxygenation

et al. 2021

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Ischemia-reperfusion injury is the commonest form of acute kidney injury (AKI). Tubular epithelial cell senescence contributes to incomplete recovery from AKI and predisposes to subsequent chronic kidney disease. In cultures of primary proximal renal tubular epithelial cells (RPTECs) subjected to anoxia or reoxygenation, we evaluated the role of indoleamine 2,3-dioxygenase 1 (IDO) in cellular senescence. Proteins of interest were assessed with Western blotting or enzyme-linked immunosorbent assay or histochemically. Under anoxia or reoxygenation, IDO expression and activity were increased. Moreover, the two IDO-derived pathways, the general control nonderepressible 2 kinase (GCN2K) pathway and the aryl-hydrocarbon receptor (AhR) pathway, were also activated. A DNA damage response (DDR) took place and led to increased levels of the cell-cycle inhibitors p21 and p16, and senescence-associated β-galactosidase (SA-β-Gal) activity. Cell proliferation was inhibited, and more IL-6 was produced. The IDO inhibitor 1-DL-methyl-tryptophan ameliorated the DDR; decreased p21, p16, and SA-β-Gal activity; restored cell proliferation; and decreased IL-6 production. The AhR inhibitor CH223191 did not affect the above parameters. In conclusion, anoxia and the subsequent reoxygenation upregulate IDO. IDO depletes tryptophan and activates GCN2K. The latter enhances the anoxia- or reoxygenation-induced DDR, resulting in increased p21 and p16 expression and eventually leading to RPTEC senescence. Since cellular senescence affects AKI outcome, the role of IDO in cellular senescence and the possible therapeutic role of IDO inhibitors deserve further investigation.

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“…Many researchers have suggested that IDO2 could be an effective therapeutic target to treat inflammatory autoimmunity, while IDO1 has recently been under intense research focused on cancer immunotherapy. A few IDO1 inhibitors have been reported, some of which, including epacadostat, BMS986205, indoximod, and PF-06840003, among others, have advanced into clinical trials for cancer treatment [100].…”

Section: Major Enzymes Of Kynurenine Pathwaymentioning

confidence: 99%

The Kynurenine Pathway as a Potential Target for Neuropathic Pain Therapy Design: From Basic Research to Clinical Perspectives

Ciapała

Mika

Rojewska

2021

IJMS

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Accumulating evidence suggests the key role of the kynurenine pathway (KP) of the tryptophan metabolism in the pathogenesis of several diseases. Despite extensive research aimed at clarifying the mechanisms underlying the development and maintenance of neuropathic pain, the roles of KP metabolites in this process are still not fully known. Although the function of the peripheral KP has been known for several years, it has only recently been acknowledged that its metabolites within the central nervous system have remarkable consequences related to physiology and behavior. Both the products and metabolites of the KP are involved in the pathogenesis of pain conditions. Apart from the neuroactive properties of kynurenines, the KP regulates several neurotransmitter systems in direct or indirect ways. Some neuroactive metabolites are known to have neuroprotective properties (kynurenic acid, nicotinamide adenine dinucleotide cofactor), while others are toxic (3-hydroxykynurenine, quinolinic acid). Numerous animal models show that modulation of the KP may turn out to be a viable target for the treatment of diseases. Importantly, some compounds that affect KP enzymes are currently described to possess analgesic properties. Additionally, kynurenine metabolites may be useful for assessing response to therapy or as biomarkers in therapeutic monitoring. The following review describes the molecular site of action and changes in the levels of metabolites of the kynurenine pathway in the pathogenesis of various conditions, with a particular emphasis on their involvement in neuropathy. Moreover, the potential clinical implications of KP modulation in chronic pain therapy as well as the directions of new research initiatives are discussed.

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Indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors in clinical trials for cancer immunotherapy

Cited by 230 publications

References 97 publications

NK Cell Regulation in Cervical Cancer and Strategies for Immunotherapy

NK Cell Regulation in Cervical Cancer and Strategies for Immunotherapy

The Role of Indoleamine 2,3-Dioxygenase in Renal Tubular Epithelial Cells Senescence under Anoxia or Reoxygenation

The Kynurenine Pathway as a Potential Target for Neuropathic Pain Therapy Design: From Basic Research to Clinical Perspectives

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