Abstract
Many patients with cancer suffer from anemia, depression, and an impaired quality of life (QoL). These patients often also show decreased plasma tryptophan levels and increased kynurenine concentrations in parallel with elevated concentrations of Th1 type immune activation marker neopterin. In the course of anti-tumor immune response, the pro-inflammatory cytokine interferon gamma (IFN-γ) induces both, the enzyme indoleamine 2,3-dioxygenase (IDO) to degrade tryptophan and the enzyme GTP-cyclohydrolase I to form neopterin. High neopterin concentrations as well as an increased kynurenine to tryptophan ratio (Kyn/Trp) in the blood of cancer patients are predictive for a worse outcome. Inflammation-mediated tryptophan catabolism along the kynurenine pathway is related to fatigue and anemia as well as to depression and a decreased QoL in patients with solid tumors. In fact, enhanced tryptophan breakdown might greatly contribute to the development of anemia, fatigue, and depression in cancer patients. IDO activation and stimulation of the kynurenine pathway exert immune regulatory mechanisms, which may impair anti-tumor immune responses. In addition, tumor cells can degrade tryptophan to weaken immune responses directed against them. High IDO expression in the tumor tissue is associated with a poor prognosis of patients. The efficiency of IDO-inhibitors to inhibit cancer progression is currently tested in combination with established chemotherapies and with immune checkpoint inhibitors. Inflammation-mediated tryptophan catabolism and its possible influence on the development and persistence of anemia, fatigue, and depression in cancer patients are discussed.
Highlights
Cancer is a leading cause of death and disability worldwide with an increasing prevalence
Acute myeloid leukemia Up-regulation of IDO1 expression upon IFN-γ stimulation was related to an impaired overall survival
Inflammation-induced Trp breakdown in cancer patients is considered to play a key role in the pathophysiology of tumor immune tolerance
Summary
Cancer is a leading cause of death and disability worldwide with an increasing prevalence. Patients with malignant diseases often have sustained systemic immune activation, which is linked to tumor progression and a poor clinical outcome [1, 2]. Immune activation is an important mechanism to prevent carcinogenesis. This mechanism does not seem to work properly in patients with advanced cancer. Tumor cells are able to escape immune-mediated elimination by leukocytes due to loss of antigenicity and/or immunogenicity and. Tryptophan Breakdown in Cancer Patients by creating an immunosuppressive microenvironment and by blocking anti-tumor immune response [3]. Tryptophan (Trp) metabolism appears to play an important role within the tumor microenvironment [4]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
