肿瘤坏死因子相关凋亡诱导配体参与自然杀伤细胞介导的以及γ干扰素依赖的皮下肿瘤生长抑制作用。

Involvement of tumor necrosis factor-related apoptosis-inducing ligand in NK cell-mediated and IFN-gamma-dependent suppression of subcutaneous tumor growth.

作者信息

Takeda K, Smyth M J, Cretney E, Hayakawa Y, Yamaguchi N, Yagita H, Okumura K

机构信息

Department of Immunology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, Japan.

出版信息

Cell Immunol. 2001 Dec 15;214(2):194-200. doi: 10.1006/cimm.2001.1896.

DOI:10.1006/cimm.2001.1896

PMID:12088418

Abstract

Natural killer (NK) cells and interferon- (IFN) gamma have been implicated in immune surveillance against tumor development. Here we show tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), which is a type II membrane protein belonging to the TNF family and plays a critical role in the NK cell-mediated and IFN-gamma-dependent suppression of subcutaneous growth of TRAIL-sensitive tumors. Administration of a neutralizing monoclonal antibody against TRAIL promoted outgrowth of subcutaneously inoculated TRAIL-sensitive tumors (L929, LB27.4, and Renca) but not TRAIL-resistant tumors (P815 and B16). Such a protective effect of TRAIL against TRAIL-sensitive tumors was abrogated in NK cell-depleted or IFN-gamma-deficient mice. These results suggested a substantial role of TRAIL as the effector molecule that eliminates subcutaneously developing TRAIL-sensitive tumors.

摘要

自然杀伤（NK）细胞和干扰素-γ（IFN-γ）参与了针对肿瘤发生的免疫监视。在此我们表明，肿瘤坏死因子相关凋亡诱导配体（TRAIL），它是一种属于TNF家族的II型膜蛋白，在NK细胞介导的以及IFN-γ依赖的对TRAIL敏感肿瘤皮下生长的抑制中起关键作用。给予抗TRAIL的中和单克隆抗体促进了皮下接种的TRAIL敏感肿瘤（L929、LB27.4和Renca）的生长，但对TRAIL抗性肿瘤（P815和B16）无效。TRAIL对TRAIL敏感肿瘤的这种保护作用在NK细胞耗竭或IFN-γ缺陷的小鼠中被消除。这些结果表明TRAIL作为消除皮下生长的TRAIL敏感肿瘤的效应分子发挥了重要作用。