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

Abstract

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 Treg cells in the blood of gastric carcinoma patients compared to healthy individuals, and depletion of Treg cells from the blood of these patients prior to TEM restored T cell migration. The effect of Treg cells was largely dependent on cell-cell contact, but not on IL-10 or TGF-β. In addition, the presence of Treg cells led to reduced T cell attachment to endothelium and decreased production of T cell-recruiting chemokines during TEM. In conclusion, Treg cell-mediated reduction of T cell TEM may reduce T cell recruitment in patients with epithelial malignancies, thereby hampering anti-tumour responses. © 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.