4.4 Review

The immunosuppressive role of indoleamine 2, 3-dioxygenase in glioblastoma: mechanism of action and immunotherapeutic strategies

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Summary: Blocking tryptophan catabolism mediated by IDO1 and TDO shows promise for sensitising cancer patients to immune checkpoint blockade. Understanding the immune-regulatory function of tryptophan catabolism could lead to optimized therapeutic strategies. Tryptophan may act as a rheostat of kynurenine-mediated immunosuppression by competing for entry into immune T-cells.

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Summary: IDO1 is an important heme enzyme involved in cancer immune escape, associated with poor prognosis in various cancers, and currently undergoing clinical trials with multiple drugs. The development of IDO1 degraders using PROTAC technology presents a novel therapeutic approach.

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Tumor Cell IDO Enhances Immune Suppression and Decreases Survival Independent of Tryptophan Metabolism in Glioblastoma

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Summary: This study reveals that nonenzymatic tumor cell IDO activity decreases survival and increases CFH and FHL-1 expression in human GBM independent of Trp metabolism. The increased intra-tumoral CFH and FHL-1 levels are associated with poorer survival in glioma patients. Like IDO effects, GBM cell FHL-1 expression increases intratumoral Treg and myeloid-derived suppressor cells while decreasing overall survival in mice with GBM, providing a new therapeutic target for GBM patients.

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Summary: The TRP-KYN metabolic pathway is responsible for the breakdown of over 95% of tryptophan. Activation of this pathway by immune responses can lead to various diseases. Immunomodulators in the pathway help the immune system achieve a tolerogenic state, leading to chronic low-grade inflammation.

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Acyclovir inhibition of IDO to decrease Tregs as a glioblastoma treatment adjunct

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Antimicrobial and immunoregulatory properties of human tryptophan 2,3-dioxygenase

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Indoleamine 2,3-dioxygenase-2; a new enzyme in the kynurenine pathway

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Autocrine glutamate signaling promotes glioma cell invasion

Susan A. Lyons et al.

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Plasmacytoid dendritic cells from mouse tumor-draining lymph nodes directly activate mature Tregs via indoleamine 2,3-dioxygenase

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Kynurenic acid has a dual action on AMPA receptor responses

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NMDA antagonist inhibits the extracellular signal-reglulated kinase pathway and suppresses cancer growth

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IDO expression by dendritic cells: Tolerance and tryptophan catabolism

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Increased cortical kynurenate content in schizophrenia

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Similarities and differences in the neuronal death processes activated by 3OH-kynurenine and quinolinic acid

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