Modulation of CD103 Expression on Human Colon Carcinoma-Specific CTL

Abstract

Recent results have shown a correlation between survival and frequency of tumor-infiltrating T cells in colorectal cancer patients. However, the mechanisms controlling the ability of human T lymphocytes to infiltrate colon carcinoma remain unclear. Although, it is known that expression of the integrin CD103αE/β7 by intraepithelial lymphocytes controls the retention of lymphocytes in epithelial layers, very little is known about the expression of intestinal homing receptors in human T lymphocytes. In particular, it remains unknown whether expression of CD103/β7 by human colon cancer-specific T lymphocytes is controlled by recognition of tumor Ags and is imprinted during T cell priming, facilitating its expression during memory T cell activation. In this study, we demonstrate that expression of CD103/β7 in human colon carcinoma-specific CTL is synergistically enhanced by the simultaneous TGF-β1 stimulation and Ag recognition. These results were confirmed by using a panel of human CTL clones. Finally, we show that priming of naive CD8+ T cells in the presence of TGF-β1 ensures up-regulation of CD103/β7 in recall responses, at concentrations of TGF-β1 significantly lower than those required by memory T cells primed in the absence of TGF-β1. These results indicate a role of TGF-β1 during T cell priming in modulating expression of CD103/β7 and controlling retention of human memory CD8+ T cells into tumor epithelium.