Indoleamine-2,3 dioxygenase: a fate-changer of the tumor microenvironment

Azimnasab-Sorkhabi, Parviz; Soltani-Asl, Maryam; Yoshinaga, Túlio Teruo; Dagli, M.L.; Massoco, Cristina de Oliveira; Kfoury, José Roberto

doi:10.1007/s11033-023-08469-3

Cited by 8 publications

(4 citation statements)

References 100 publications

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“…In melanoma, TAMs regulate the expression of hypoxia-inducible factor (HIF)2a in tumor areas where the level of oxygen is low, facilitating tumor cell survival [ 272 ]. Further, TAMs release indoleamine 2,3-dioxygenase (IDO) an intracellular enzyme that primes the breakdown of tryptophan in the tumor microenvironment reducing lymphocyte proliferation because of the strong dependence on this amino acid [ 273 ]. Changes in melanoma behavior require adaptative modification of neighboring keratinocytes as evidenced by the hyperplastic features of the epidermis surrounding nodular melanoma [ 274 ].…”

Section: Melanoma and Non-melanoma Skin Cancer Microenvironments: Sim...mentioning

confidence: 99%

Skin Cancer Microenvironment: What We Can Learn from Skin Aging?

D’Arino,

Caputo,

Eibenschutz

et al. 2023

IJMS

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Aging is a natural intrinsic process associated with the loss of fibrous tissue, a slower cell turnover, and a reduction in immune system competence. In the skin, the continuous exposition of environmental factors superimposes extrinsic damage, mainly due to ultraviolet radiation causing photoaging. Although not usually considered a pathogenic event, photoaging affects cutaneous biology, increasing the risk of skin carcinogenesis. At the cellular level, aging is typified by the rise of senescence cells a condition characterized by reduced or absent capacity to proliferate and aberrant hyper-secretory activity. Senescence has a double-edged sword in cancer biology given that senescence prevents the uncontrolled proliferation of damaged cells and favors their clearance by paracrine secretion. Nevertheless, the cumulative insults and the poor clearance of injured cells in the elderly increase cancer incidence. However, there are not conclusive data proving that aged skin represents a permissive milieu for tumor onset. On the other hand, tumor cells are capable of activating resident fibroblasts onto a pro-tumorigenic phenotype resembling those of senescent fibroblasts suggesting that aged fibroblasts might facilitate cancer progression. This review discusses changes that occur during aging that can prime neoplasm or increase the aggressiveness of melanoma and non-melanoma skin cancer.

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Section: Melanoma and Non-melanoma Skin Cancer Microenvironments: Sim...mentioning

confidence: 99%

Skin Cancer Microenvironment: What We Can Learn from Skin Aging?

D’Arino,

Caputo,

Eibenschutz

et al. 2023

IJMS

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“…Indoleamine 2,3-dioxygenase (IDO), an enzyme that degrades tryptophan in the kynurenine pathway, has been shown to enhance immunosuppression. 65 Anti-CTLA-4 therapy facilitated IDO induction in resistant HCC tumors but was invalid in tumors that are sensitive to ICP inhibitors. Furthermore, IDO inhibitors were effective in treating high IDO-induced HCC-resistant tumors in hepatic orthotopic and subcutaneous models.…”

Section: The Regulation Of Ctla-4 Signals In the Development Of Hccmentioning

confidence: 99%

Blockade of PD‐1 and CTLA‐4: A potent immunotherapeutic approach for hepatocellular carcinoma

Hou,

Xu,

et al. 2023

BioFactors

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Immune checkpoints (ICPs) can promote tumor growth and prevent immunity‐induced cancer cell apoptosis. Fortunately, targeting ICPs, such as programmed cell death 1 (PD‐1) or cytotoxic T lymphocyte associated protein 4 (CTLA‐4), has achieved great success in the past few years and has gradually become an effective treatment for cancers, including hepatocellular carcinoma (HCC). However, many patients do not respond to ICP therapy due to acquired resistance and recurrence. Therefore, clarifying the specific mechanisms of ICP in the development of HCC is very important for enhancing the efficacy of anti‐PD‐1 and anti‐CTLA‐4 therapy. In particular, antigen presentation and interferon‐γ (IFN‐γ) signaling were reported to be involved in the development of resistance. In this review, we have explained the role and regulatory mechanisms of ICP therapy in HCC pathology. Moreover, we have also elaborated on combinations of ICP inhibitors and other treatments to enhance the antitumor effect. Collectively, recent advances in the pharmacological targeting of ICPs provide insights for the development of a novel alternative treatment for HCC.

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“…Meanwhile, metabolites such as pyridine carboxylic acid and kynurenine induce T cell apoptosis due to their obvious toxic effects. The suppression of effector T cells allows the tumor to escape host immune surveillance, thus creating an immunosuppressive microenvironment [25,26]. Furthermore, IDO acts on the dendritic cells (DCs) surface and interacts with regulatory T cells (Tregs), producing immunosuppressive effects due to their high expression, through the direct contact or production of suppressive cytokines.…”

Section: Immune Regulation Of Ido Pathwaymentioning

confidence: 99%

Indoleamine 2,3-Dioxygenase (IDO) Activity: A Perspective Biomarker for Laboratory Determination in Tumor Immunotherapy

Yang

Zhang

2023

Biomedicines

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Indoleamine 2,3-dioxygenase 1 (IDO1) is a heme enzyme involved in catalyzing the conversion of tryptophan (Trp) into kynurenine (Kyn) at the first rate-limiting step in the kynurenine pathway of L-tryptophan metabolism. It has been found to be involved in several biological functions such as aging, immune microorganism, neurodegenerative and infectious diseases, and cancer. IDO1 plays an important role in immune tolerance by depleting tryptophan in the tumor microenvironment and inhibiting the proliferation of effector T cells, which makes it an important emerging biomarker for cancer immunotherapy. Therefore, the research and development of IDO1 inhibitors are of great importance for tumor therapy. Of interest, IDO activity assays are of great value in the screening and evaluation of inhibitors. Herein, we mainly review the biological functions of IDO1, immune regulation, key signaling molecules in the response pathway, and the development of IDO1 inhibitors in clinical trials. Furthermore, this review provides a comprehensive overview and, in particular, a discussion of currently available IDO activity assays for use in the evaluation of IDO inhibitors in human blood. We believe that the IDO activity is a promising biomarker for the immune escape and laboratory evaluation of tumor immunotherapy.

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Indoleamine-2,3 dioxygenase: a fate-changer of the tumor microenvironment

Cited by 8 publications

References 100 publications

Skin Cancer Microenvironment: What We Can Learn from Skin Aging?

Skin Cancer Microenvironment: What We Can Learn from Skin Aging?

Blockade of PD‐1 and CTLA‐4: A potent immunotherapeutic approach for hepatocellular carcinoma

Indoleamine 2,3-Dioxygenase (IDO) Activity: A Perspective Biomarker for Laboratory Determination in Tumor Immunotherapy

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