Li Jing, Yang Fan, Wei Feng, Ren Xiubao
Department of Immunology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
Department of Biotherapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
Oncotarget. 2017 Jul 8;8(39):66656-66667. doi: 10.18632/oncotarget.19105. eCollection 2017 Sep 12.
Tumors are closely related to chronic inflammation, during which there are various changes in inflammatory sites, such as immune cells infiltration, pro-inflammation cytokines production, and interaction between immune cells and tissue cells. Besides, substances, released from both tissue cells attacked by exogenous etiologies, also act on local cells. These changes induce a dynamic and complex microenvironment favorable for tumor growth, invasion, and metastasis. The toll-like receptor 4 (TLR4) is the first identified member of the toll-like receptor family that can recognize pathogen-associated molecular patterns (PAMPs) and damage-associated molecular pattern (DAMPs). TLR4 expresses not only on immune cells but also on tumor cells. Accumulating evidences demonstrated that the activation of TLR4 in tumor microenvironment can not only boost the anti-tumor immunity but also give rise to immune surveillance and tumor progression. This review will summarize the expression and function of TLR4 on dendritic cells (DCs), tumor-associated macrophages (TAMs), T cells, myeloid-derived suppressor cells (MDSCs), tumor cells as well as stromal cells in tumor microenvironment. Validation of the multiple role of TLR4 in tumors could primarily pave the road for the development of anti-tumor immunotherapy.
肿瘤与慢性炎症密切相关,在此过程中炎症部位会发生各种变化,如免疫细胞浸润、促炎细胞因子产生以及免疫细胞与组织细胞之间的相互作用。此外,受到外源性病因攻击的组织细胞释放的物质也作用于局部细胞。这些变化诱导了一个有利于肿瘤生长、侵袭和转移的动态复杂微环境。Toll样受体4(TLR4)是Toll样受体家族中首个被鉴定出的成员,它能够识别病原体相关分子模式(PAMPs)和损伤相关分子模式(DAMPs)。TLR4不仅在免疫细胞上表达,也在肿瘤细胞上表达。越来越多的证据表明,肿瘤微环境中TLR4的激活不仅能增强抗肿瘤免疫力,还会引发免疫监视和肿瘤进展。本综述将总结TLR4在肿瘤微环境中的树突状细胞(DCs)、肿瘤相关巨噬细胞(TAMs)、T细胞、髓源性抑制细胞(MDSCs)、肿瘤细胞以及基质细胞上的表达和功能。验证TLR4在肿瘤中的多重作用可能首先为抗肿瘤免疫治疗的发展铺平道路。