Tokumoto Mao, Tanaka Hiroaki, Tauchi Yukie, Tamura Tatsuro, Toyokawa Takahiro, Kimura Kenjiro, Muguruma Kazuya, Yashiro Masakazu, Maeda Kiyoshi, Hirakawa Kosei, Ohira Masaichi
Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan.
Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan
Anticancer Res. 2017 Jun;37(6):2875-2883. doi: 10.21873/anticanres.11640.
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.
We examined the impact of cancer cells on the phenotype and production of cytokines of LECs derived from tumor-draining lymph nodes.
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.
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.
背景/目的:淋巴结转移是胃癌患者最重要的预后因素。越来越多的证据表明,淋巴管内皮细胞(LEC)调节免疫反应。本研究的目的是检测LEC对CD4 T细胞活化的影响。
我们检测了癌细胞对肿瘤引流淋巴结来源的LEC的表型和细胞因子产生的影响。
我们发现LEC抑制CD4 T细胞产生细胞因子,如IL-2、IL-10和INF-γ。当LEC和CD4 T细胞与胃癌细胞系OCUM12的细胞共培养时,LEC的程序性死亡配体1(PD-L1)和吲哚胺2,3-双加氧酶(IDO)的mRNA表达显著上调。
淋巴结内LEC可能是诱导胃癌免疫耐受和促进通过淋巴管转移的关键因素。