Beneficial and Detrimental Roles of NLRs in Carcinogenesis.

Beneficial and Detrimental Roles of NLRs in Carcinogenesis.
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DOI:
10.3389/fimmu.2013.00370
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发表时间:
2013
影响因子:
7.3
通讯作者:
Sutterwala FS
Sutterwala FS
中科院分区:
医学2区
文献类型:
--
作者:
Janowski AM;Kolb R;Zhang W;Sutterwala FS

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炎症在肿瘤的发生中起着关键作用,并可能导致致癌突变、肿瘤促进和血管生成。促肿瘤炎症是由许多因素驱动的,包括促炎细胞因子IL-1、β和IL-18的存在。炎症小体的激活是IL-1β和IL-18分泌的主要来源之一。炎性小体是由多种蛋白质组成的复合体,激活后由半胱氨酸蛋白酶β-1介导IL-1和IL-18的加工和分泌。一些炎症体,包括NLRP3、NLRC4和NLRP6,都与肿瘤的发生有关。然而,炎性小体在不同类型的癌症中扮演着不同的角色,反映了肿瘤发生过程中炎症的复杂性。了解炎性小体激活在肿瘤发生的特定阶段以及癌症免疫治疗中的作用将有助于确定新的治疗靶点,从而改善癌症患者的治疗策略。在这里,我们将讨论在了解NLRs调控癌症发生的机制方面的最新进展。
Inflammation plays a critical role in tumorigenesis and can contribute to oncogenic mutations, tumor promotion, and angiogenesis. Tumor-promoting inflammation is driven by many factors including the presence of the pro-inflammatory cytokines interleukin (IL)-1β and IL-18. One major source of IL-1β and IL-18 secretion is through the activation of inflammasomes. Inflammasomes are multi-protein complexes that upon activation lead to the processing and secretion of IL-1β and IL-18 mediated by the cysteine protease caspase-1. Several inflammasomes, including NLRP3, NLRC4, and NLRP6, have been implicated in tumorigenesis. However, inflammasomes play divergent roles in different types of cancer reflecting the complexity of inflammation during tumorigenesis. Understanding the role of inflammasome activation during specific stages of tumorigenesis and also during cancer immunotherapy will help identify novel therapeutic targets that could improve treatment strategies for cancer patients. Here we will discuss recent advances in understanding the mechanism by which NLRs regulate carcinogenesis.
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