Effect of Indoleamine 2,3 Dioxygenase Inhibitor on the Cytotoxic Activity of Tumour-infiltrating Lymphocytes

Naour, S. Le; Knol, Anne-Chantal; Pandolfino, Marie‐Christine; Khammari, Amir; Dréno, Brigitte

doi:10.2340/00015555-3285

Cited by 1 publication

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References 12 publications

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“…It enhances immune tolerance by an increase in a KYN and its downstream metabolites levels within the tumor microenvironment [ 51 , 52 ]. KYN induces general control nonderepressible-2 kinase and mammalian target of rapamycin kinase pathways, which reduce the immune response [ 41 , 53 , 54 , 55 , 56 ]. Other effects of KYN include increased TH1 and effector T cells anergy and apoptosis rate and T regulatory cells (T regs) immunosuppressive activity [ 57 , 58 , 59 , 60 ].…”

Section: The Role Of the Kynurenine Pathway In Neoplastic Processesmentioning

confidence: 99%

Kynurenines as a Novel Target for the Treatment of Malignancies

2021

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Malignancies are unquestionably a significant public health problem. Their effective treatment is still a big challenge for modern medicine. Tumors have developed a wide range of mechanisms to evade an immune and therapeutic response. As a result, there is an unmet clinical need for research on solutions aimed at overcoming this problem. An accumulation of tryptophan metabolites belonging to the kynurenine pathway can enhance neoplastic progression because it causes the suppression of immune system response against cancer cells. They are also involved in the development of the mechanisms responsible for the resistance to antitumor therapy. Kynurenine belongs to the most potent immunosuppressive metabolites of this pathway and has a significant impact on the development of malignancies. This fact prompted researchers to assess whether targeting the enzymes responsible for its synthesis could be an effective therapeutic strategy for various cancers. To date, numerous studies, both preclinical and clinical, have been conducted on this topic, especially regarding the inhibition of indoleamine 2,3-dioxygenase activity and their results can be considered noteworthy. This review gathers and systematizes the knowledge about the role of the kynurenine pathway in neoplastic progression and the findings regarding the usefulness of modulating its activity in anticancer therapy.

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