Macrophages reprogrammed by lung cancer microparticles promote tumor development via release of IL-1β.
Macrophages reprogrammed by lung cancer microparticles promote tumor development via release of IL-1β.
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DOI：
10.1038/s41423-019-0313-2
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发表时间：
2020-12
影响因子：
24.1
通讯作者：
Huang B
中科院分区：
文献类型：
--
作者：
Chen J;Sun W;Zhang H;Ma J;Xu P;Yu Y;Fang H;Zhou L;Lv J;Xie J;Liu Y;Tang K;Huang B
尽管它们相互拮抗，但由于肿瘤和免疫细胞的相互作用，炎症和免疫抑制在肿瘤微环境中共存，但其潜在机制仍不清楚。以前，我们表明，肿瘤细胞衍生的微粒诱导M2表型，其特征在于肿瘤浸润性巨噬细胞的免疫抑制。在这里，我们进一步表明，肺癌微粒（L-MP）诱导巨噬细胞释放一种关键的促炎细胞因子IL-1β，从而促进肺癌的发展。其潜在机制涉及L-MP激活TLR 3和NLRP 3炎性体。更重要的是，酪氨酸激酶抑制剂治疗诱导的L-MP还诱导人巨噬细胞释放IL-1β，从而在人源化小鼠模型中产生促肿瘤作用。这些发现表明，除了它们的抗炎作用之外，L-MP还在肿瘤浸润性巨噬细胞中诱导促炎表型，促进炎症和免疫抑制肿瘤微环境的发展。
Despite their mutual antagonism, inflammation and immunosuppression coexist in tumor microenvironments due to tumor and immune cell interactions, but the underlying mechanism remains unclear. Previously, we showed that tumor cell-derived microparticles induce an M2 phenotype characterized by immunosuppression in tumor-infiltrating macrophages. Here, we further showed that lung cancer microparticles (L-MPs) induce macrophages to release a key proinflammatory cytokine, IL-1β, thus promoting lung cancer development. The underlying mechanism involves the activation of TLR3 and the NLRP3 inflammasome by L-MPs. More importantly, tyrosine kinase inhibitor treatment-induced L-MPs also induce human macrophages to release IL-1β, leading to a tumor-promoting effect in a humanized mouse model. These findings demonstrated that in addition to their anti-inflammatory effect, L-MPs induce a proinflammatory phenotype in tumor-infiltrating macrophages, promoting the development of inflammatory and immunosuppressive tumor microenvironments.
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影响因子：
29.7
作者：
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影响因子：
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DOI：
10.1111/j.1600-0897.2011.00995.x
发表时间：
2011-10-01
影响因子：
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作者：
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作者：
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