CSF1R-dependent myeloid cells are required for NK-mediated control of metastasis

被引：37

作者：

Beffinger, Michal ^{[1
]}

Tallon de Lara, Paulino ^{[1
]}

Tugues, Sonia ^{[1
]}

Vermeer, Marijne ^{[1
]}

Montagnolo, Yannick ^{[1
]}

Ohs, Isabel ^{[1
]}

Cecconi, Virginia ^{[1
]}

Lucchiari, Giulia ^{[1
]}

Gagliardi, Aron ^{[1
]}

Misljencevic, Nikola ^{[1
]}

Sutton, James ^{[2
,4
]}

Spoerri, Roman ^{[3
]}

Becher, Burkhard ^{[1
]}

Gupta, Anurag ^{[1
,5
]}

van den Broek, Maries ^{[1
]}

机构：

[1] Univ Zurich, Inst Expt Immunol, Winterthurerstr 190, CH-8057 Zurich, Switzerland

[2] Novartis Inst Biomed Res, Emeryville, CA USA

[3] ETH, Inst Microbiol, Zurich, Switzerland

[4] IDEAYA San Francisco, San Francisco, CA USA

[5] Univ Hosp Zurich, Visceral & Transplantat Surg, Zurich, Switzerland

来源：

JCI INSIGHT | 2018年 / 3卷 / 10期

基金：

瑞士国家科学基金会;

关键词：

NATURAL-KILLER-CELLS; BREAST-CANCER METASTASIS; STIMULATING FACTOR-I; MACROPHAGE POLARIZATION; TRANS-PRESENTATION; IL-15; ACTIVITY; TUMOR; INHIBITION; MONOCYTES; BLOCKADE;

D O I：

10.1172/jci.insight.97792

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Myeloid leukocytes are essentially involved in both tumor progression and control. We show that neo-adjuvant treatment of mice with an inhibitor of CSF1 receptor (CSF1R), a drug that is used to deplete tumor-associated macrophages, unexpectedly promoted metastasis. CSF1R blockade indirectly diminished the number of NK cells due to a paucity of myeloid cells that provide the survival factor IL-15 to NK cells. Reduction of the number of NK cells resulted in increased seeding of metastatic tumor cells to the lungs but did not impact on progression of established metastases. Supplementation of mice treated with CSF1R-inhibitor with IL-15 restored numbers of NK cells and diminished metastasis. Our data suggest that CSF1R blockade should be combined with administration of IL-15 to reduce the risk of metastasis.

引用

页数：14

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