Targeting indoleamine-2,3-dioxygenase in cancer: Scientific rationale and clinical evidence
| Autor: | Paolo Puccetti, Rita Chiari, Francesca Fallarino, Vanessa Bianconi, Biagio Ricciuti, Giulia Costanza Leonardi, Amirhossein Sahebkar, Matteo Pirro, Sara Baglivo |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
medicine.medical_treatment Navoximod Indoleamine-2 03 medical and health sciences 0302 clinical medicine Immune system Immunity Neoplasms Immune Tolerance medicine Animals Humans Indoleamine-Pyrrole 2 3 -Dioxygenase Pharmacology (medical) Indoleamine 2 3-dioxygenase Cancer Pharmacology Tumor microenvironment business.industry Indoximod Immunotherapy medicine.disease Epacadostat Indoleamine-2 3-dioxygenase Immune checkpoint Clinical trial 3-dioxygenase 030104 developmental biology 030220 oncology & carcinogenesis Cancer research Tumor Escape business |
| Zdroj: | Pharmacology & Therapeutics. 196:105-116 |
| ISSN: | 0163-7258 |
| DOI: | 10.1016/j.pharmthera.2018.12.004 |
| Popis: | Immunotherapy through immune checkpoint blockers (ICBs) is quickly transforming cancer treatment by improving patients' outcomes. However, innate and acquired resistance to ICBs remain a major challenge in clinical settings. Indoleamine 2,3-dioxygenases (IDOs) are enzymes involved in tryptophan catabolism with a central immunosuppressive function within the tumor microenvironment. IDOs are over-expressed in cancer patients and have increasingly been associated with worse outcomes and a poor prognosis. Preclinical data have shown that combining IDO and checkpoint inhibition might be a valuable strategy to improve the efficacy of immunotherapy. Currently, several IDO inhibitors have been evaluated in clinical trials, showing favorable pharmacokinetic profiles and promising efficacy. This review describes the mechanisms involved in IDO-mediated immune suppression and its role in cancer immune escape, focusing on the potential clinical application of IDO inhibitors as an immunotherapy strategy for cancer treatment. |
| Databáze: | OpenAIRE |
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