CSF1R-dependent myeloid cells are required for NK‑mediated control of metastasis
Michal Beffinger, … , Anurag Gupta, Maries van den Broek
Michal Beffinger, … , Anurag Gupta, Maries van den Broek
Published May 17, 2018
Citation Information: JCI Insight. 2018;3(10):e97792. https://doi.org/10.1172/jci.insight.97792.
View: Text | PDF
Research Article Immunology Oncology

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

Abstract

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.

Authors

Michal Beffinger, Paulino Tallón de Lara, Sònia Tugues, Marijne Vermeer, Yannick Montagnolo, Isabel Ohs, Virginia Cecconi, Giulia Lucchiari, Aron Gagliardi, Nikola Misljencevic, James Sutton, Roman Spörri, Burkhard Becher, Anurag Gupta, Maries van den Broek

×

Figure 4

Exogenous IL-15 prevents CSF1Ri-induced loss of NK cells and metastasis.

Options: View larger image (or click on image) Download as PowerPoint
Exogenous IL-15 prevents CSF1Ri-induced loss of NK cells and metastasis....
(A) Experimental timeline. (B) Number of circulating NK cells defined as CD45.2+CD3–NK1.1+NKp46+ live singlets on day 3. Each symbol represents an individual mouse. Ctrl, n = 9; CSF1Ri, n = 10; IL-15c, n = 5; CSF1Ri + IL-15c, n = 5. Mean ± SD. ***P < 0.005 (1-way ANOVA with Bonferroni’s correction). A representative experiment of 2 is shown. (C) Quantification of tumor burden in the lungs by bioluminescence. Each symbol represents an individual mouse. Ctrl, n = 9; CSF1Ri, n = 10; IL-15c, n = 5; CSF1Ri + IL-15c, n = 5. Mean ± SEM. *P < 0.05 (1-way ANOVA with Bonferroni’s correction). A representative experiment of 2 is shown. (D) Representative bioluminescence images of resected lungs at the endpoint.