Activation of the kynurenine pathway predicts poor outcome in patients with clear cell renal cell carcinoma

Phase 1 investigation of lenalidomide/rituximab plus outcomes of lenalidomide maintenance in relapsed CNS lymphoma

“…High serum kynurenine and increasing kynurenine/tryptophan (K/T) ratios are established biomarkers of IDO activity and correlate with tumor aggressiveness in a variety of malignancies. [39][40][41][42][43] In particular, in aggressive lymphomas, baseline elevated kynurenine concentration in serum has reproducibly been demonstrated to be an independent adverse prognostic factor associated with short overall survival in both systemic DLBCL (kynurenine concentration, .1.5 mM) 43,44 and in adult T-cell leukemia/lymphoma (kynurenine concentration, .2 mM). 45 We performed serial analysis of kynurenine and tryptophan concentrations in ventricular CSF in phase 1 subjects treated with lenalidomide.…”

Immune checkpoints indoleamine 2,3‐dioxygenase 1 and programmed death‐ligand 1 in oral mucosal dysplasia

“…Immune checkpoints are used by cancer cells to escape from immune cell destruction, mainly by CD8 + T cells and NK cells . The presence of distinct immune checkpoint molecules, such as indoleamine 2,3‐dioxygenase 1 (IDO1) and programmed death‐ligand 1 (PD‐L1) in tumors, are considered as negative prognostic factors . Furthermore, immune checkpoint inhibitors, such as PD‐1/PD‐L1 axis inhibitors, are already in use as anticancer therapies .…”

“…9 The presence of distinct immune checkpoint molecules, such as indoleamine 2,3-dioxygenase 1 (IDO1) and programmed death-ligand 1 (PD-L1) in tumors, are considered as negative prognostic factors. [10][11][12] Furthermore, immune checkpoint inhibitors, such as PD-1/PD-L1 axis inhibitors, are already in use as anticancer therapies. 13 Other immune checkpoint inhibitors, such as IDO1, are still in clinical trials.…”

The urea cycle enzymes act as metabolic suppressors in clear cell renal cell carcinoma

“…Recent studies have investigated novel molecular mechanisms involved in the RCC pathogenesis, and have identified potential biomarkers with a role in early diagnosis, risk assessment, and outcome prediction. Different molecular markers such as CA 15-3, αKlotho, RKIP and many metabolic enzymes have been investigated, but none of these factors is used in the clinical management of kidney cancer patients (4)(5)(6)(7)(8)(9)(10)(11).…”

“…In recent years, a series of metabolic adaptations involving the accumulation of uncommon oncometabolites has been described (9,(19)(20)(21). In this scenario, a recent study showed that in clear cell RCC (ccRCC)-the most common kidney cancer subtype-the expression of multiple urea cycle enzymes was strongly repressed, suggesting a tumor suppressant role in normal physiological conditions (22).…”