The spleen plays an immunosuppressive role in patients with gastric cancer: involvement of CD62L+ cells and TGF-beta.

Abstract

CD62L is the human homologue of the murine lymphocyte homing receptor, mel-14. We investigated CD62L + cells in the spleen from patients with gastric cancer. Flow cytometric analysis revealed that CD62L + cells were decreased in the peripheral blood, but inversely increased in the spleen in parallel with disease progression in gastric cancer patients. The increased CD62L+ cells resided in the CD4+ suppressor-inducer phenotype, and the removal of CD62L+ cells from spleen cells resulted in a decrease of concanavalin-A-induced suppressor activity in vitro in one-way allogeneic mixed lymphocyte reaction. The CD62L+ cells included CD4+CD25+ regulatory T cells. The culture supernatant of CD62L + cells showed TGF-beta activity that permitted anchorage-independent growth of normal rat kidney (NRK) cells in a soft agar. TGF-beta activity was more significantly detectable in the splenic vein than in the peripheral blood, and TGF-beta mRNA was detectable in the spleen from advanced gastric cancer patients. These results suggest that CD62L+ cells migrate into the spleen with disease progression of gastric cancer and serve as suppressor-inducer cells with TGF-beta production to induce regulatory T cells, contributing to disease-associated immunosuppression in advanced gastric cancer patients.