Targeting inflammasome/IL-1 pathways for cancer immunotherapy.
Targeting inflammasome/IL-1 pathways for cancer immunotherapy.
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DOI：
10.1038/srep36107
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发表时间：
2016-10-27
影响因子：
4.6
通讯作者：
Li Z
中科院分区：
文献类型：
--
作者：
Guo B;Fu S;Zhang J;Liu B;Li Z
炎症微环境已被证明在肿瘤发生的各个阶段发挥重要作用，包括起始、生长和转移。炎性小体是产生活性IL-1β的关键先天免疫途径，IL-1β是一种有效的炎症细胞因子。尽管炎性小体对宿主防御病原体和自身免疫性疾病至关重要，但它们在肿瘤进展中的作用仍然存在争议。本研究结果表明，炎症小体和IL-1β通路促进了动物和人乳腺癌模型的肿瘤生长和转移。我们发现肿瘤进展与炎性体的激活和原发和转移部位IL-1β水平升高有关。缺乏炎性体成分的小鼠表现出肿瘤生长和肺转移显著减少。此外，炎性体激活促进髓系细胞如髓源性抑制细胞（MDSCs）和肿瘤相关巨噬细胞（tam）向肿瘤微环境的浸润。重要的是，用IL-1R拮抗剂（IL-Ra）阻断IL-1R可以抑制肿瘤的生长和转移，同时减少骨髓细胞的积累。我们的研究结果表明，靶向肿瘤微环境中的炎性体/IL-1通路可能为癌症的治疗提供一种新的途径。
The inflammatory microenvironment has been shown to play important roles in various stages of tumor development including initiation, growth, and metastasis. The inflammasome is a critical innate immune pathway for the production of active IL-1β, a potent inflammatory cytokine. Although inflammasomes are essential for host defense against pathogens and contribute to autoimmune diseases, their role in tumor progression remains controversial. Here, our results demonstrate that the inflammasome and IL-1β pathway promoted tumor growth and metastasis in animal and human breast cancer models. We found that tumor progression was associated with the activation of inflammasome and elevated levels of IL-1β at primary and metastatic sites. Mice deficient for inflammasome components exhibited significantly reduced tumor growth and lung metastasis. Furthermore, inflammasome activation promoted the infiltration of myeloid cells such as myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) into tumor microenvironments. Importantly, blocking IL-1R with IL-1R antagonist (IL-Ra) inhibited tumor growth and metastasis accompanied by decreased myeloid cell accumulation. Our results suggest that targeting the inflammasome/IL-1 pathway in tumor microenvironments may provide a novel approach for the treatment of cancer.
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影响因子：
29.7
作者：
Davis BK;Wen H;Ting JP
通讯作者：
Ting JP
影响因子：
7.8
作者：
Cassel SL;Joly S;Sutterwala FS
通讯作者：
Sutterwala FS
影响因子：
8.7
作者：
Broz P;Monack DM
通讯作者：
Monack DM
影响因子：
1.3
作者：
Gorbachev, Anton V.;Fairchild, Robert L.
通讯作者：
Fairchild, Robert L.
DOI：
10.1073/pnas.1016814108
发表时间：
2010-12-14
影响因子：
11.1
作者：
Hu, Bo;Elinav, Eran;Flavell, Richard A.
通讯作者：
Flavell, Richard A.