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

JCI Insight
Michal BeffingerMaries van den Broek

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.

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Citations

Feb 19, 2019·Journal of Leukocyte Biology·Claire E OlingyCatherine C Hedrick
May 16, 2019·Immunotherapy·Joanna KowalJohanna A Joyce
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Methods Mentioned

BETA
dissecting
flow cytometry
FACS
FCS

Software Mentioned

GraphPad QuickCalcs
FlowJo
GraphPad Prism
GraphPad

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