Table 1.
Altered tryptophan metabolism in different cancer types and its relations to disease severity, progression, and survival.
| Cancer type | Tryptophan metabolism within tumor tissues | Tryptophan metabolism in the peripheral blood | ||
|---|---|---|---|---|
| Findings | References | Findings | References | |
| Acute myeloid leukemia | Up-regulation of IDO1 expression upon IFN-γ stimulation was related to an impaired overall survival | Folgiero et al. (5) | Increased Kyn levels were associated with a shorter overall survival | Mabuchi et al. (6) |
| Increased IDO1 mRNA expression was correlated with an impaired overall survival | Fukuno et al. (7) | Kyn/Trp ratio was increased and associated with a shorter overall survival | Corm et al. (8) | |
| Increased IDO1 mRNA expression was related to an impaired overall survival and relapse-free survival | Chamuleau et al. (9) | |||
| Increased IDO1 expression inhibited T-cell proliferation | Tang et al. (10) | |||
| Breast cancer | High IDO1 expression was associated with TNM stage, histological grade, lymph node metastasis, progression-free survival, and overall survival | Wei et al. (11) | Trp levels predict tumor progression and were associated with overall survival | Eniu et al. (12) |
| Up-regulation of IDO1, TDO2, and KMO expression was found | Heng et al. (13) | Low Trp levels and an increased Kyn/Trp ratio were found | Lyon et al. (14) | |
| IDO1 expression increased with higher tumor stages | Isla Larrain et al. (15) | Increased Kyn/Trp ratio was associated with higher tumor grade and elevated neopterin levels | Girgin et al. (16) | |
| Increased IDO1 expression promotes tumor progression and is associated with an impaired overall survival | Chen et al. (17) | |||
| Higher IDO1 expression was associated with an impaired overall survival in estrogen receptor positive group | Soliman et al. (18) | |||
| Higher IDO1 expression was predictive for a better overall survival | Jacquemier et al. (19) | |||
| IDO1 expression was increased and correlated with tumor stages and lymph node metastasis | Yu et al. (20) | |||
| Colorectal cancer | Increased IDO1 expression upon IFN-γ stimulation correlated with metastasis rate and an impaired overall survival | Ferdinande et al. (21) | Kyn/Trp ratio was increased and related to high neopterin levels and lymph node metastasis | Engin et al. (22) |
| Increased IDO1 expression was associated with an impaired overall survival | Gao et al. (23) | Reduced Trp levels and an increased Kyn/Trp ratio was related to high neopterin levels and an impaired QoL | Huang et al. (24) | |
| Increased IDO1 expression upon IFN-γ stimulation correlated with reduced T-cell infiltration, higher metastasis rate and an impaired overall survival | Brandacher et al. (25) | |||
| Gastrointestinal tumors | Increased IDO1 expression in esophageal cancer tissues was associated with differentiation grade, TNM stage, lymph node metastasis, and an impaired overall survival | Jia et al. (26) | Trp levels were decreased and associated with elevated neopterin levels | Iwagaki et al. (27) |
| High IDO1 expression was a negative prognostic factor | Laimer et al. (28) | |||
| Increased IDO1 expression in esophageal cancer cells was related to disease progression and an impaired overall survival | Zhang et al. (29) | |||
| Glioma | Up-regulation of IDO1, IDO2, and KMO expression upon IFN-γ stimulation was found | Adams et al. (30) | High Kyn/Trp ratio was correlated with an impaired overall survival | Zhai et al. (31) |
| Increased IDO1 expression was correlated with an impaired overall survival | Mitsuka et al. (32) | Low Trp, KYNA and QUIN levels, and a high Kyn/Trp ratio were found | Adams et al. (30) | |
| Downregulation of IDO1 expression was associated with a better overall survival | Wainwright et al. (33) | |||
| Gynecological cancer | Marginal IDO expression in patients in early stage cervical cancer predicted a favorable outcome | Heeren et al. (34) | Increased Kyn/Trp ratio correlated with advanced disease, poor response to therapy, and an impaired overall survival | Gostner et al. (35) |
| Increased IDO expression in endometrial carcinoma cells correlated with reduced T-cell infiltration and an impaired disease-specific survival | de Jong et al. (36) | Kyn/Trp ratio was increased and related to lymph node metastasis, FIGO stage, tumor size, parametrial invasion, and poor disease-specific survival in patients with cervical cancer | Ferns et al. (37) | |
| Increased IDO expression in cervical cancer cells was associated with higher tumor stage, lymph node metastasis, and an impaired overall survival | Inaba et al. (38) | Kyn/Trp ratio was increased in patients with ovarian cancer and associated with higher FIGO stages | Sperner-Unterweger et al. (39) | |
| High IDO1 expression in ovarian carcinoma cells correlated with reduced T-cell infiltration and an impaired overall survival | Inaba et al. (40) | Kyn/Trp ratio was increased | de Jong et al. (41) | |
| High IDO1 expression in endometrial cancer tissues was related to reduced T-cell infiltration, lymph node-metastasis, and poor progression-free survival | Ino et al. (42) | Increased QUIN levels and reduced KYNA levels were found in patients with primary ovarian cancer | Fotopoulou et al. (43) | |
| Increased IDO1 expression in ovarian cancer cells was correlated with impaired survival in patients with serous-type ovarian cancer | Okamoto et al. (44) and Takao et al. (45) | Elevated Trp levels and a decreased Kyn/Trp ratio was found and associated with elevated neopterin levels | Schroecksnadel et al. (46) | |
| High IDO1 expression in endometrial carcinoma cells was related to an impaired progression-free and overall survival | Ino et al. (47) | |||
| Hepatocellular carcinoma | Increased IDO1 expression was associated with T-cell infiltration and an impaired overall survival | Li et al. (48) | ||
| Increased KMO expression was correlated with an impaired overall survival and an increased time to recurrence | Jin et al. (49) | |||
| Increased IDO1 expression upon IFN-γ stimulation correlates with metastasis rate and an impaired overall survival | Pan et al. (50) | |||
| Increased IDO1 expression in tumor infiltrating cells was associated with an increased progression-free survival | Ishio et al. (51) | |||
| Kidney cancer | Up-regulation of IDO1 expression upon IFN-γ stimulation was found | Trott et al. (52) | Kyn/Trp ratio was increased and associated with a poorer progression-free survival | Lucarelli et al. (53) |
| High IDO1 mRNA levels were associated with an increased overall survival | Riesenberg et al. (54) and Yuan et al. (55) | |||
| Lung cancer | IDO1 expression was increased and correlated with TNM stage and lymph node-metastasis | Tang et al. (56) | Low Trp levels and a high Kyn/Trp ratio were associated with an increased lung cancer risk in the EPIC study; In the International Lung cancer cohort consortium (5,364 smoking-matched case- control pairs) the highest quintiles of kynurenine, Kyn/Trp, quinolinic acid and neopterin were associated with a 20–30% higher risk and tryptophan with a 15% lower risk of lung cancer |
Chuang et al. (57) Huang et al. (58) |
| Enhanced Kyn production and increased TDO2 expression by cancer-associated fibroblasts was found | Hsu et al. (59) | Post-induction chemotherapy increased Kyn/Trp ratio was associated with an impaired progression-free and overall survival | Creelan et al. (60) | |
| No associations between IDO1 expression and clinicopathological parameters were found | Karanikas et al. (61) | Low Trp levels and a high Kyn/Trp ratio were found and associated with high neopterin levels, low hemoglobin levels, fatigue, and QoL | Kurz et al. (62) | |
| Increased IDO1 expression by infiltrating tumor cells was related to an impaired overall survival | Astigiano et al. (63) | Low Trp levels and a high Kyn/Trp ratio were found and associated with elevated neopterin levels | Engin et al. (64) | |
| Low Trp levels and a higher Kyn/Trp ratio were found and related to tumor progression | Suzuki et al. (65) | |||
| Lymphoma | High IDO1 expression in tumor infiltrating immune cells was related to an increased overall survival | Nam et al. (66) | High Kyn levels and Kyn/Trp ratio were found and associated with tumor progression and a shorter overall survival in patients with adult T-cell leukemia/lymphoma | Masaki et al. (67) |
| Up-regulation of IDO1 in non-Hodgkin lymphoma tissues was related to tumor progression, higher serum LDH and an impaired overall survival | Liu et al. (68) | High Kyn levels correlated with an impaired overall survival | Yoshikawa et al. (69) | |
| IDO1 expression was increased in stroma cells of Hodgkin lymphoma and correlated with an impaired overall survival | Choe et al. (70) | Low Trp levels and high Kyn levels were found and related to a shorter overall survival in patients with adult T-cell leukemia/lymphoma | Giusti et al. (71) | |
| High IDO1 expression in non-Hodgkin lymphoma tissues was related to a lower remission rates and an impaired overall survival | Ninomiya et al. (72) | |||
| IDO1 mRNA expression was increased in adult T-cell leukemia/lymphoma cells | Hoshi et al. (73) | |||
| Melanoma | Increased IDO1 expression in nodal metastases was associated with an impaired overall survival | Pelak et al. (74) | Low Trp levels and a high Kyn/Trp ratio were found and associated with high neopterin levels and an impaired overall survival | Weinlich et al. (75) |
| Increased IDO1 expression in nodal metastases was associated with clinical recurrence | Ryan et al. (76) | Patients who developed major depression during IFN-α therapy had a significantly higher Kyn/Trp ratio | Capuron et al. (77) | |
| Increased IDO1 expression in sentinel lymph nodes correlated with an impaired progression-free and overall survival | Speeckaert et al. (78) | |||
| Increased IDO1 expression in nodal metastases was associated with a poor survival | Brody et al. (79) | |||
| Osteosarcoma | High IDO1 expression correlated with an impaired metastasis-free and overall survival | Urakawa et al. (80) | ||
| Pancreatic cancer | Increased IDO1 expression upon IFN-γ stimulation correlated with lymph node metastasis and an impaired overall survival | Zhang et al. (81) | Higher HAA/HK ratio was associated with a reduced pancreatic cancer risk | Huang et al. (82) |
| Prostate cancer | IDO1 expression was increased and correlated with serum Kyn/Trp ratio | Feder-Mengus et al. (83) | High Kyn levels were associated with an impaired cancer-related survival | Pichler et al. (2) |
| Thyroid carcinoma | IDO1 expression was increased and associated with tumor aggressiveness | Moretti et al. (84) | ||