Iron Induces Anti-tumor Activity in Tumor-Associated Macrophages.
Iron Induces Anti-tumor Activity in Tumor-Associated Macrophages.
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DOI：
10.3389/fimmu.2017.01479
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发表时间：
2017
影响因子：
7.3
通讯作者：
Muckenthaler MU
中科院分区：
文献类型：
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作者：
Costa da Silva M;Breckwoldt MO;Vinchi F;Correia MP;Stojanovic A;Thielmann CM;Meister M;Muley T;Warth A;Platten M;Hentze MW;Cerwenka A;Muckenthaler MU
肿瘤相关巨噬细胞（TAM）通常有助于维持肿瘤生长并介导肿瘤微环境（TME）中的免疫抑制。在这里，我们确定了一个子集的铁负载，促炎TAM定位在出血区的TME。在非小细胞肺癌患者中，载铁TAM（iTAM）的发生与肿瘤大小减小相关。离体实验证实，暴露于溶血性红细胞（RBC）的TAM转化为能够直接杀死肿瘤细胞的促炎性巨噬细胞。这种抗肿瘤作用也可以通过氧化铁纳米颗粒引起。当在体内测试时，与对照相比，注射这种氧化铁纳米颗粒的肿瘤导致肿瘤尺寸显著减小。这些结果鉴定了溶血性RBC和铁作为TME中的新参与者，其抑制TAM发挥直接的抗肿瘤效应子功能。因此，将铁递送至TAM作为促进抗癌免疫应答的简单辅助治疗策略出现。
Tumor-associated macrophages (TAMs) frequently help to sustain tumor growth and mediate immune suppression in the tumor microenvironment (TME). Here, we identified a subset of iron-loaded, pro-inflammatory TAMs localized in hemorrhagic areas of the TME. The occurrence of iron-loaded TAMs (iTAMs) correlated with reduced tumor size in patients with non-small cell lung cancer. Ex vivo experiments established that TAMs exposed to hemolytic red blood cells (RBCs) were converted into pro-inflammatory macrophages capable of directly killing tumor cells. This anti-tumor effect could also be elicited via iron oxide nanoparticles. When tested in vivo, tumors injected with such iron oxide nanoparticles led to significantly smaller tumor sizes compared to controls. These results identify hemolytic RBCs and iron as novel players in the TME that repolarize TAMs to exert direct anti-tumor effector function. Thus, the delivery of iron to TAMs emerges as a simple adjuvant therapeutic strategy to promote anti-cancer immune responses.