Pre-metastatic cancer exosomes induce immune surveillance by patrolling monocytes at the metastatic niche.
Pre-metastatic cancer exosomes induce immune surveillance by patrolling monocytes at the metastatic niche.
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DOI：
10.1038/s41467-017-01433-3
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发表时间：
2017-11-06
影响因子：
16.6
通讯作者：
Volpert OV
中科院分区：
文献类型：
--
作者：
Plebanek MP;Angeloni NL;Vinokour E;Li J;Henkin A;Martinez-Marin D;Filleur S;Bhowmick R;Henkin J;Miller SD;Ifergan I;Lee Y;Osman I;Thaxton CS;Volpert OV
转移性癌症会产生外泌体，这些外泌体调节远端微环境中的转移前微环境，以促进转移。相比之下，我们在此表明，低转移性黑色素瘤细胞的外泌体能够有效抑制向肺部的转移。这些“非转移性”外泌体通过刺激骨髓中Ly6C低表达的巡逻单核细胞（PMo）的扩增来激发先天免疫反应，然后这些细胞通过招募自然杀伤细胞以及巨噬细胞依赖TRAIL对黑色素瘤细胞的杀伤作用，在转移前微环境中清除癌细胞。这些过程需要诱导Nr4a1转录因子，并且依赖于外泌体表面的色素上皮衍生因子（PEDF）。重要的是，从非转移性原发性黑色素瘤患者中分离出的外泌体具有类似的抑制肺转移的能力。因此，这项研究表明，转移前肿瘤产生外泌体，这些外泌体通过触发免疫监视引发广泛的依赖PMo的先天免疫反应，从而在转移前微环境中清除癌细胞。
外泌体是细胞外囊泡，可促进肿瘤发展和转移。在此，作者表明癌症外泌体也可能发挥抑制功能；事实上，来自非转移性黑色素瘤细胞的外泌体可导致巡逻单核细胞的募集，这些细胞在转移前微环境中清除癌细胞。
Metastatic cancers produce exosomes that condition pre-metastatic niches in remote microenvironments to favor metastasis. In contrast, here we show that exosomes from poorly metastatic melanoma cells can potently inhibit metastasis to the lung. These “non-metastatic” exosomes stimulate an innate immune response through the expansion of Ly6Clow patrolling monocytes (PMo) in the bone marrow, which then cause cancer cell clearance at the pre-metastatic niche, via the recruitment of NK cells and TRAIL-dependent killing of melanoma cells by macrophages. These events require the induction of the Nr4a1 transcription factor and are dependent on pigment epithelium-derived factor (PEDF) on the outer surface of exosomes. Importantly, exosomes isolated from patients with non-metastatic primary melanomas have a similar ability to suppress lung metastasis. This study thus demonstrates that pre-metastatic tumors produce exosomes, which elicit a broad range of PMo-reliant innate immune responses via trigger(s) of immune surveillance, causing cancer cell clearance at the pre-metastatic niche. Exosomes are extracellular vesicles that can favor tumor development and metastasis. Here, the authors show that cancer exosomes may also exert a suppressive function; in fact, exosomes from non-metastatic melanoma cells can lead to the recruitment of patrolling monocytes, which clear cancer cells at the pre-metastatic niche.
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影响因子：
7.3
作者：
Andreu Z;Yáñez-Mó M
通讯作者：
Yáñez-Mó M
影响因子：
16
作者：
Imai T;Takahashi Y;Nishikawa M;Kato K;Morishita M;Yamashita T;Matsumoto A;Charoenviriyakul C;Takakura Y
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Takakura Y
影响因子：
3.2
作者：
Czernek L;Düchler M
通讯作者：
Düchler M
影响因子：
11.2
作者：
Bobrie, Angelique;Krumeich, Sophie;Thery, Clotilde
通讯作者：
Thery, Clotilde
影响因子：
21.3
作者：
Costa-Silva B;Aiello NM;Ocean AJ;Singh S;Zhang H;Thakur BK;Becker A;Hoshino A;Mark MT;Molina H;Xiang J;Zhang T;Theilen TM;García-Santos G;Williams C;Ararso Y;Huang Y;Rodrigues G;Shen TL;Labori KJ;Lothe IM;Kure EH;Hernandez J;Doussot A;Ebbesen SH;Grandgenett PM;Hollingsworth MA;Jain M;Mallya K;Batra SK;Jarnagin WR;Schwartz RE;Matei I;Peinado H;Stanger BZ;Bromberg J;Lyden D
通讯作者：
Lyden D