SCS macrophages suppress melanoma by restricting tumor-derived vesicle-B cell interactions

被引：260

作者：

Pucci, Ferdinando ^{[1
,7
]}

Garris, Christopher ^{[1
,2
]}

Lai, Charles P. ^{[3
,8
]}

Newton, Andita ^{[1
]}

Pfirschke, Christina ^{[1
]}

Engblom, Camilla ^{[1
,2
]}

Alvarez, David ^{[4
]}

Sprachman, Melissa ^{[1
]}

Evavold, Charles ^{[1
,2
]}

Magnuson, Angela ^{[1
]}

von Andrian, Ulrich H. ^{[4
]}

Glatz, Katharina ^{[5
]}

Breakefield, Xandra O. ^{[3
]}

Mempel, Thorsten R. ^{[6
]}

Weissleder, Ralph ^{[1
]}

Pittet, Mikael J. ^{[1
]}

机构：

[1] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol,Res Inst, Boston, MA 02114 USA

[2] Harvard Univ, Sch Med, Grad Program Immunol, Boston, MA 02115 USA

[3] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Res Inst, Charlestown, MA 02129 USA

[4] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA

[5] Univ Basel Hosp, Inst Pathol, CH-4031 Basel, Switzerland

[6] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis,Res Inst, Charlestown, MA 02129 USA

[7] Torque Therapeut Inc, Cambridge, MA 02142 USA

[8] Natl Tsing Hua Univ, Inst Biomed Engn, Hsinchu, Taiwan

来源：

SCIENCE | 2016年 / 352卷 / 6282期

基金：

加拿大健康研究院;

关键词：

SUBCAPSULAR SINUS MACROPHAGES; LYMPH-NODES; INFLAMMATION; EXOSOMES; MICROVESICLES; INFECTION; RNA;

D O I：

10.1126/science.aaf1328

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Tumor-derived extracellular vesicles (tEVs) are important signals in tumor-host cell communication, yet it remains unclear how endogenously produced tEVs affect the host in different areas of the body. We combined imaging and genetic analysis to track melanoma-derived vesicles at organismal, cellular, and molecular scales to show that endogenous tEVs efficiently disseminate via lymphatics and preferentially bind subcapsular sinus (SCS) CD169(+) macrophages in tumor-draining lymph nodes (tdLNs) in mice and humans. The CD169(+) macrophage layer physically blocks tEVdissemination but is undermined during tumor progression and by therapeutic agents. A disrupted SCS macrophage barrier enables tEVs to enter the lymph node cortex, interact with B cells, and foster tumor-promoting humoral immunity. Thus, CD169(+) macrophages may act as tumor suppressors by containing tEV spread and ensuing cancer-enhancing immunity.

引用

页码：242 / 246

页数：5

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