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


Beffinger, Michal; Tallón de Lara, Paulino; Tugues, Sònia; Vermeer, Marijne; Montagnolo, Yannick; Ohs, Isabel; Cecconi, Virginia; Lucchiari, Giulia; Gagliardi, Aron; Misljencevic, Nikola; Sutton, James; Spörri, Roman; Becher, Burkhard; Gupta, Anurag; van den Broek, Maries (2018). CSF1R-dependent myeloid cells are required for NK‑mediated control of metastasis. Journal of clinical investigation insight, 3(10):e97792.

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.

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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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Experimental Immunology
08 Research Priority Programs > Translational Cancer Research
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:17 May 2018
Deposited On:21 Nov 2018 17:10
Last Modified:14 Apr 2019 05:50
Publisher:American Society for Clinical Investigation
ISSN:2379-3708
OA Status:Green
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1172/jci.insight.97792
PubMed ID:29769439

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