Published online Mar 28, 2015. doi: 10.3748/wjg.v21.i12.3636
Peer-review started: September 12, 2014
First decision: October 29, 2014
Revised: December 1, 2014
Accepted: January 16, 2015
Article in press: January 16, 2015
Published online: March 28, 2015
AIM: To evaluate how Helicobacter pylori (H. pylori) is able to evade the immune response and whether it enhances systemic immune tolerance against colorectal cancer.
METHODS: This prospective randomized study involved 97 consecutive colorectal cancer patients and 108 cancer-free patients with extra-digestive diseases. Colorectal cancer and cancer-free patients were assigned into subgroups according to H. pylori IgG seropositivity. Exposure to H. pylori was determined by IgG seropositivity which was detected by enzyme linked immunoassay (ELISA). Serum neopterin levels were measured by ELISA. Serum tryptophan, kynurenine, and urinary biopterin concentrations were measured by high performance liquid chromatography. Serum nitrite levels were detected spectrophotometrically. Serum indoleamine 2,3-dioxygenase activity was estimated by the kynurenine to tryptophan ratio and by assessing the correlation between serum neopterin concentrations and the kynurenine to tryptophan ratio. The frequencies of increased serum kynurenine to tryptophan ratio of H. pylori seronegative and seropositive colorectal cancer subgroups were estimated by comparing them with the average kynurenine to tryptophan ratio of H. pylori seronegative tumor-free patients.
RESULTS: Compared with respective controls, in both H. pylori seronegative and seropositive colorectal cancer patients, while serum tryptophan levels were decreased (controls vs patients; seronegative: 20.37 ± 0.89 μmol/L vs 15.71 ± 1.16 μmol/L, P < 0.05; seropositive: 20.71 ± 0.81 μmol/L vs 14.97 ± 0.79 μmol/L, P < 0.01) the kynurenine to tryptophan ratio was significantly increased (controls vs patients; seronegative: 52.85 ± 11.85 μmol/mmol vs 78.91 ± 8.68 μmol/mmol, P < 0.01, seropositive: 47.31 ± 5.93 μmol/mmol vs 109.65 ± 11.50 μmol/mmol, P < 0.01). Neopterin concentrations in cancer patients were significantly elevated compared with controls (P < 0.05). There was a significant correlation between serum neopterin levels and kynurenine/tryptophan in control and colorectal cancer patients groups (rs = 0.494, P = 0.0001 and rs = 0.293, P = 0.004, respectively). Serum nitrite levels of H. pylori seropositive cancer cases were significantly decreased compared with seropositive controls (controls vs patients; 26.04 ± 2.39 μmol/L vs 20.41 ± 1.48 μmol/L, P < 0.05) The decrease in the nitrite levels of H. pylori seropositive cancer patients may be attributed to excessive formation of peroxynitrite and other reactive nitrogen species.
CONCLUSION: A significantly high kynurenine/tryptophan suggested that H. pylori may support the immune tolerance leading to cancer development, even without an apparent upper gastrointestinal tract disease.
Core tip: Persistent inflammation of the stomach induced by Helicobacter pylori (H. pylori) can have consequences on the rest of the body. Despite the vigorous innate and adaptive immune response against the bacterium, H. pylori escape and evade host responses by a variety of mechanisms. Low tryptophan levels and increased concentrations of its degradation product, kynurenine, may be directly involved in diminished T-cell responsiveness to antigenic stimulation in cancer. H. pylori seropositive colorectal cancer patients with significantly higher kynurenine/tryptophan and reduced nitric oxide suggested that H. pylori might support immune tolerance leading to cancer development, even in patients without an apparent upper gastrointestinal tract disease.