CD4+CD25high regulatory T cells reduce T cell transendothelial migration in cancer patients

Cell-mediated immunity is thought to be the main mechanism of anti-tumour responses of the host, but it is not known if cancer disease affects T cell recruitment from blood to tissues. Therefore, we compared Heliobacter pylori-induced T cell transendothelial migration (TEM) in H. pylori-infected gastric carcinoma patients, colon and lung carcinoma patients and healthy volunteers. H. pylori induced significant T cell migration from all groups. However, there was a dramatic reduction of T cell TEM in gastric carcinoma patients (80%) compared to healthy individuals. A similarly reduced transmigration was also seen in colon and lung carcinoma patients. We found significantly increased frequencies of T-reg cells in the blood of gastric carcinoma patients compared to healthy individuals, and depletion of T-reg cells from the blood of these patients prior to TEM restored T cell migration. The effect of T-reg cells was largely dependent on cell-cell. contact, but not on IL-10 or TGF-beta. In addition, the presence of T-reg cells led to reduced T cell attachment to endothelium and decreased production of T cell-recruiting chemokines during TEM. In conclusion, T-reg cell-mediated reduction of T cell TEM may reduce T cell recruitment in patients with epithelial malignancies, thereby hampering anti-tumour responses.