T Cell Trafficking Plays an Essential Role in Tumor Immunity

Distinct populations of effector memory T cells use different homing receptors to traffic to skin and gut (1). Whether tissue selective T cells are needed for early rejection of a neoplasm growing in these tissues remains an open question (2). We chose to study an allogeneic tumor model because growth of such a fully mismatched tumor would signify a profound immune deficit. We implanted allogeneic tumor cells in the skin or gut of mice deficient in either α(1,3) fucosyltransferases IV and VII, enzymes critical for generating E- selectin ligands on skin homing T cells, or β7 integrin, a component of the α4β7 integrin ligand for the mucosal adressin MAdCAM. During the first 9 days after tumor implantation FucTVII(−/−) mice showed a profoundly impaired capacity to reject tumors growing in skin, but readily rejected tumors implanted in the gut. Rejection of tumors in skin was even more impaired in mice deficient in both FucTIV and FucTVII. This impairment was corrected by infusion of T cells from normal mice. By contrast, β7 integrin(−/−) mice showed profoundly impaired rejection of tumors in gut, but no defect in skin tumor rejection. These differences were unrelated to antigen recognition or effector function of T cells, since all strains of mice were capable of generating tumor specific CTL’s in vitro against the tumor cell line used in vivo. These results demonstrate that T cell homing defects in vivo impair immune surveillance of peripheral epithelial tissues in a specific and selective fashion.