Trial watch: IDO inhibitors in cancer therapy.
Ontology highlight
ABSTRACT:
SUBMITTER: Le Naour J
PROVIDER: S-EPMC7466863 | biostudies-literature | 2020 Jun
REPOSITORIES: biostudies-literature
Publications
Trial watch: IDO inhibitors in cancer therapy.
Le Naour Julie J Galluzzi Lorenzo L Zitvogel Laurence L Kroemer Guido G Vacchelli Erika E
Oncoimmunology 20200614 1
Indoleamine 2,3-dioxygenase 1 (IDO1) catalyzes the first, rate-limiting step of the so-called "kynurenine pathway", which converts the essential amino acid <i>L-</i>tryptophan (Trp) into the immunosuppressive metabolite <i>L-</i>kynurenine (Kyn). While expressed constitutively by some tissues, IDO1 can also be induced in specific subsets of antigen-presenting cells that ultimately favor the establishment of immune tolerance to tumor antigens. At least in part, the immunomodulatory functions of I ...[more]
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Project description:Indoleamine 2,3-dioxigenase 1 (IDO1) is the main enzyme that catalyzes the first, rate-limiting step of the so-called "kynurenine pathway", i.e., the metabolic cascade that converts the essential amino acid L-tryptophan (Trp) into L-kynurenine (Kyn). IDO1, which is expressed constitutively by some tissues and in an inducible manner by specific subsets of antigen-presenting cells, has been shown to play a role in the establishment and maintenance of peripheral tolerance. At least in part, this reflects the capacity of IDO1 to restrict the microenvironmental availability of Trp and to favor the accumulation of Kyn and some of its derivatives. Also, several neoplastic lesions express IDO1, providing them with a means to evade anticancer immunosurveillance. This consideration has driven the development of several IDO1 inhibitors, some of which (including 1-methyltryptophan) have nowadays entered clinical evaluation. In animal tumor models, the inhibition of IDO1 by chemical or genetic interventions is indeed associated with the (re)activation of therapeutically relevant anticancer immune responses. This said, several immunotherapeutic regimens exert robust clinical activity in spite of their ability to promote the expression of IDO1. Moreover, 1-methyltryptophan has recently been shown to exert IDO1-independent immunostimulatory effects. Here, we summarize the preclinical and clinical studies testing the antineoplastic activity of IDO1-targeting interventions.
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