模式识别受体与肿瘤微环境研究进展

Recent progress in the research on pattern recognition receptors and tumor microenvironment

肿瘤微环境的组成与肿瘤发生发展的关系备受瞩目,免疫系统参与肿瘤微环境形成并在其中发挥重要作用,天然免疫细胞对肿瘤的免疫监视以及免疫耐受的形成具有双向功能。模式识别受体(pattern recognition receptors,PRRs)是天然免疫细胞识别病毒、细菌等病原体以启动免疫与炎症过程的受体,在肿瘤免疫中也发挥双向的调控功能,其既能维持宿主寄生菌群平衡、清除死亡或突变细胞以抑制肿瘤发生,又能诱导慢性炎症、形成炎性微环境以促进肿瘤发生;既能识别危险信号启动天然免疫杀伤及后续的获得性免疫应答以抑制肿瘤进程,又能识别肿瘤释放的内源性配体以促进抑制性细胞亚群和细胞因子的产生,进而诱导肿瘤的免疫耐受与免疫抑制。此外,多种肿瘤细胞亦表达多种PRRs,肿瘤细胞本身PRR通路参与了肿瘤的发生、发展。本文将阐述肿瘤微环境中PRRs及其配体表达的特点,重点分析PRRs在肿瘤免疫调控中发挥的双向调控功能,以期为肿瘤免疫微环境形成的认识及肿瘤免疫治疗的设计提供新的视角。

Tumor microenvironment has attracted significant research attentions worldwide. It is now generally accepted that the immune system is one of major components in tumor microenvironment and is involved in almost all processes of tumor development and progression. Innate immunity plays dual roles in immune surveillance and immune tolerance in the interaction of host and tumors. As the sensors for innate immunity,pattern recognition receptors( PRRs) can recognize virus,bacteria and other pathogens to initiate the immune responses. PRRs are also bifacial in the regulation of tumor immunity. They can inhibit tumorigenesis through maintaining the host- microflora homeostasis and removing the death or mutant cells and recognize danger signals to induce immunogenic tumor cell death to inhibit tumor progression on one hand,they can also contribute to tumorigenesis in settings of chronic inflammation and induction of regulatory cell populations and immunosuppressive cytokines to facilitate tumor growth on the other hand. In addition,tumor cells also express various PRRs,which are involved in tumor development and progression. In this review,we summarize the expression of PRRs and their ligands in tumor microenvironment,with a particular focus on the dual characters of PRRs in tumor immunity.