Johns Hopkins School of Medicine, Baltimore, Maryland.
Virginia Cancer Specialists (VCS), Fairfax, Virginia.
Anticancer Drugs. 2019 Oct;30(9):879-885. doi: 10.1097/CAD.0000000000000832.
Inflammation is essential for our innate and adaptive immunity, but chronic inflammation can also be detrimental, playing a role in tumor development and subversion of host immunity. A multitude of proteins and cytokines are involved in chronic inflammation; interleukin-1β, in particular, has been recognized as a critical pro-inflammatory cytokine that can trigger a cascade of inflammatory mediators, promoting angiogenesis, tumor invasiveness, and metastasis. The inhibition of interleukin-1β with the antibody canakinumab was recently highlighted in a large-scale trial studying the effects of the inflammatory modulating antibody in heart disease. In this study, a marked decrease in the incidence of lung cancer (a 67% relative risk reduction) was observed in a high-risk population. Although a number of preclinical studies have demonstrated that canakinumab inhibits interleukin-1β and reduces inflammation, the question remains whether these actions positively affect both cancer incidence and recurrence. This review will summarize the role of inflammation in cancer propagation and development, discuss the biological rationale for targeting interleukin-1β in lung cancer, advocate for further investigation of the anti-inflammatory antibody canakinumab as a new attractive mechanism for future lung cancer therapy, and discuss future and ongoing trials.
炎症对于我们的先天免疫和适应性免疫至关重要，但慢性炎症也可能有害，它在肿瘤发展和宿主免疫的颠覆中发挥作用。许多蛋白质和细胞因子参与慢性炎症；特别是白细胞介素-1β，已被认为是一种关键的促炎细胞因子，可引发一连串的炎症介质，促进血管生成、肿瘤侵袭和转移。用抗体卡那单抗抑制白细胞介素-1β最近在一项研究炎症调节抗体对心脏病影响的大规模试验中得到了强调。在这项研究中，高危人群的肺癌发病率显著下降（相对风险降低 67%）。尽管许多临床前研究表明卡那单抗抑制白细胞介素-1β并减轻炎症，但仍存在疑问，即这些作用是否会积极影响癌症的发生和复发。这篇综述将总结炎症在癌症传播和发展中的作用，讨论针对肺癌中白细胞介素-1β的生物学原理，主张进一步研究抗炎抗体卡那单抗作为未来肺癌治疗的一种新的有吸引力的机制，并讨论未来和正在进行的试验。
