Immunoregulatory function of lymphatic endothelial cells in tumor-draining lymph nodes of human gastric cancer

Abstract

Background/Aim: Lymph node metastasis is the most important prognostic factor for patients with gastric cancer. Increasing evidence suggests that lymphatic endothelial cells (LECs) regulate immune responses. The aim of this study was to examine the effect of LECs on the activation of CD4+ T cells. Materials and Methods: We examined the impact of cancer cells on the phenotype and production of cytokines of LECs derived from tumor-draining lymph nodes. Results: We showed that LECs inhibited CD4+ T cell production of cytokines, such as IL-2, IL-10, and INF-γ. The mRNA expression of programmed death-ligand 1 (PD-L1) and indoleamine 2, 3-dioxygenase (IDO) by LECs were significantly up-regulated when the LECs and CD4+ T cells were co-cultured with cells of the gastric cancer cell line, OCUM12. Conclusion: Intranodal LECs may be a key player in the induction of immune tolerance against cancer and in facilitating metastasis through lymphatic vessels in gastric cancer.