The Role of Interleukin 1β in the Pathogenesis of Lung Cancer.
The Role of Interleukin 1β in the Pathogenesis of Lung Cancer.
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DOI：
10.1016/j.jtocrr.2020.100001
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发表时间：
2020-03
影响因子：
--
通讯作者：
Dubinett SM
中科院分区：
文献类型：
--
作者：
Garon EB;Chih-Hsin Yang J;Dubinett SM
慢性炎症与包括癌症在内的几种疾病的风险增加有关。由一系列细胞类型产生和维持的复杂肿瘤微环境促进肿瘤生长、血管生成和转移。炎性小体是一种多复合物胞质蛋白，可产生大部分炎症，包括细胞因子白细胞介素（IL）-1β的激活。由IL-1β产生的炎症存在于几种疾病状态中，包括动脉粥样硬化、糖尿病和关节炎。当特异性炎性小体核苷酸结合结构域样受体蛋白3诱导前IL-1β裂解为其活性形式时，IL-1β被激活。核苷酸结合结构域样受体蛋白3在肺癌中上调; IL-1β与其受体结合并激活信号通路，包括MAPK、环氧合酶和核因子-κB通路，导致巨噬细胞活化、免疫抑制性髓样细胞的瘤内蓄积以及肿瘤生长、侵袭、转移和血管生成。有证据表明IL-1β及其一些下游效应物（例如，IL-6、IL-8、C-反应蛋白、环氧合酶-2）作为包括肺癌在内的许多恶性肿瘤的预后标志物。在心肌梗死患者中进行了一项canakinumab（一种对IL-1β具有高亲和力和特异性的人免疫球蛋白Gk单克隆抗体）的III期心血管研究。该研究的亚组分析发现，canakinumab治疗以剂量依赖性方式显著降低了肺癌发病率和肺癌死亡率。一项III期试验目前正在招募参与者，以评估canakinumab作为肺癌患者辅助治疗与安慰剂的对比。其他研究正在调查早期和晚期NSCLC中已确定的抗肿瘤药物和卡那单抗的组合。
Chronic inflammation is associated with an increased risk of several diseases, including cancer. A complex tumor microenvironment created and maintained by a range of cell types promotes tumor growth, angiogenesis, and metastasis. Inflammasomes, multicomplex cytosolic proteins, generate much of this inflammation, including the activation of the cytokine interleukin (IL)-1β. Inflammation generated by IL-1β is present in several disease states, including atherosclerosis, diabetes, and arthritis. IL-1β is activated when a specific inflammasome, nucleotide-binding domain–like receptor protein 3, induces cleavage of pro–IL-1β into its active form. Nucleotide-binding domain–like receptor protein 3 is up-regulated in lung cancer; IL-1β binds to its receptor and activates signaling pathways, including the MAPK, cyclooxygenase, and nuclear factor–κB pathways, leading to macrophage activation, intratumoral accumulation of immunosuppressive myeloid cells, and tumor growth, invasiveness, metastasis, and angiogenesis. Evidence suggests a role for IL-1β and some of its downstream effectors (e.g., IL-6, IL-8, C-reactive protein, cyclooxygenase-2) as prognostic markers in many malignancies, including lung cancer. A phase III cardiovascular study of canakinumab, a human immunoglobulin Gk monoclonal antibody with high affinity and specificity for IL-1β, was conducted in patients who had a myocardial infarction. A subanalysis of this study found that treatment with canakinumab substantially reduced incident lung cancer and lung cancer mortality in a dose-dependent manner. A phase III trial is currently recruiting participants to evaluate canakinumab as adjuvant treatment versus placebo in patients with lung cancer. Other studies are investigating combinations of established antineoplastic agents and canakinumab in both early- and advanced-stage NSCLC.
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影响因子：
9.2
作者：
Dinarello, Charles A.
通讯作者：
Dinarello, Charles A.
影响因子：
--
作者：
Castro D;Moreira M;Gouveia AM;Pozza DH;De Mello RA
通讯作者：
De Mello RA
影响因子：
4.4
作者：
Carmi, Yaron;Dotan, Shahar;Voronov, Elena
通讯作者：
Voronov, Elena
影响因子：
45.3
作者：
Chaturvedi, Anil K.;Caporaso, Neil E.;Engels, Eric A.
通讯作者：
Engels, Eric A.
DOI：
10.1056/nejmoa1208962
发表时间：
2013-09-05
期刊：
The New England journal of medicine
影响因子：
--
作者：
Aberle DR;DeMello S;Berg CD;Black WC;Brewer B;Church TR;Clingan KL;Duan F;Fagerstrom RM;Gareen IF;Gatsonis CA;Gierada DS;Jain A;Jones GC;Mahon I;Marcus PM;Rathmell JM;Sicks J;National Lung Screening Trial Research Team
通讯作者：
National Lung Screening Trial Research Team