Yu Ping, Lee Youjin, Liu Wenhua, Chin Robert K, Wang Jing, Wang Yang, Schietinger Andrea, Philip Mary, Schreiber Hans, Fu Yang-Xin
The Committee on Immunology and Department of Pathology, University of Chicago, MC3083, Chicago, IL 60637, USA.
Nat Immunol. 2004 Feb;5(2):141-9. doi: 10.1038/ni1029. Epub 2004 Jan 4.
The tumor barrier comprised of nonantigenic stromal cells may contribute to the failure of tumor rejection. The tumor-necrosis factor superfamily member LIGHT (also known as TNFSF-14) is a ligand of stromal cell-expressed lymphotoxin-beta receptor and T cell-expressed herpes viral entry mediator (HVEM). Here we show that forced expression of LIGHT in the tumor environment induces a massive infiltration of naive T lymphocytes that correlates with an upregulation of both chemokine production and expression of adhesion molecules. Activation of these infiltrating T cells, possibly through HVEM, leads to the rejection of established, highly progressive tumors at local and distal sites. Our study indicates that targeting the tumor barrier may be an effective strategy for cancer immunotherapy.
由非抗原性基质细胞组成的肿瘤屏障可能导致肿瘤排斥反应失败。肿瘤坏死因子超家族成员LIGHT（也称为TNFSF - 14）是基质细胞表达的淋巴毒素β受体和T细胞表达的疱疹病毒进入介质（HVEM）的配体。在此我们表明，在肿瘤环境中强制表达LIGHT会诱导幼稚T淋巴细胞大量浸润，这与趋化因子产生和黏附分子表达的上调相关。这些浸润性T细胞的激活，可能是通过HVEM，导致在局部和远处部位已建立的、高度进展性肿瘤被排斥。我们的研究表明，靶向肿瘤屏障可能是癌症免疫治疗的一种有效策略。
