Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee.
Cancer Immunol Res. 2017 Feb;5(2):94-99. doi: 10.1158/2326-6066.CIR-16-0269. Epub 2017 Jan 16.
Inflammation affects all stages of tumorigenesis. A key signaling pathway leading to acute and chronic inflammation is through activation of the caspase-1 inflammasome. Inflammasome complexes are assembled on activation of certain nucleotide-binding domain, leucine-rich repeat-containing proteins (NLR), AIM2-like receptors, or pyrin. Of these, NLRP1, NLRP3, NLRC4, NLRP6, and AIM2 influence the pathogenesis of cancer by modulating innate and adaptive immune responses, cell death, proliferation, and/or the gut microbiota. Activation of the inflammasome and IL18 signaling pathways is largely protective in colitis-associated colorectal cancer, whereas excessive inflammation driven by the inflammasome or the IL1 signaling pathways promotes breast cancer, fibrosarcoma, gastric carcinoma, and lung metastasis in a context-dependent manner. The clinical relevance of inflammasomes in multiple forms of cancer highlights their therapeutic promise as molecular targets. In this review, we explore the crossroads between inflammasomes and the development of various tumors and discuss possible therapeutic values in targeting the inflammasome for the prevention and treatment of cancer. Cancer Immunol Res; 5(2); 94-99. ©2017 AACR.
炎症影响肿瘤发生的所有阶段。导致急性和慢性炎症的关键信号通路是通过激活半胱天冬酶-1 炎性小体。炎性小体复合物在某些核苷酸结合域、富含亮氨酸重复序列的蛋白质(NLR)、AIM2 样受体或吡喃的激活下组装。其中,NLRP1、NLRP3、NLRC4、NLRP6 和 AIM2 通过调节先天和适应性免疫反应、细胞死亡、增殖和/或肠道微生物群影响癌症的发病机制。炎性小体和 IL18 信号通路的激活在结肠炎相关结直肠癌中具有很大的保护作用,而炎性小体或 IL1 信号通路的过度炎症以依赖于上下文的方式促进乳腺癌、纤维肉瘤、胃癌和肺转移。炎性体在多种形式癌症中的临床相关性突出了它们作为分子靶点的治疗潜力。在这篇综述中,我们探讨了炎性体与各种肿瘤发展之间的交叉点,并讨论了针对炎性体的靶向治疗在癌症预防和治疗中的潜在治疗价值。Cancer Immunol Res; 5(2); 94-99. ©2017 AACR.