Tumor-derived CSF-1 induces the NKG2D ligand RAE-1δ on tumor-infiltrating macrophages

ELife
Thornton W ThompsonDavid H Raulet

Abstract

NKG2D is an important immunoreceptor expressed on the surface of NK cells and some T cells. NKG2D recognizes a set of ligands typically expressed on infected or transformed cells, but recent studies have also documented NKG2D ligands on subsets of host non-tumor cells in tumor-bearing animals and humans. Here we show that in transplanted tumors and genetically engineered mouse cancer models, tumor-associated macrophages are induced to express the NKG2D ligand RAE-1δ. We find that a soluble factor produced by tumor cells is responsible for macrophage RAE-1δ induction, and we identify tumor-derived colony-stimulating factor-1 (CSF-1) as necessary and sufficient for macrophage RAE-1δ induction in vitro and in vivo. Furthermore, we show that induction of RAE-1δ on macrophages by CSF-1 requires PI3K p110α kinase signaling. Thus, production of CSF-1 by tumor cells leading to activation of PI3K p110α represents a novel cellular and molecular pathway mediating NKG2D ligand expression on tumor-associated macrophages.

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Citations

May 18, 2019·Blood Advances·Neekun Sharma, Mary A Markiewicz
Jan 12, 2021·Frontiers in Immunology·Stefanie Maurer, Lucas Ferrari de Andrade
Aug 10, 2021·Biochimica Et Biophysica Acta. Reviews on Cancer·Fan TangXia-Wei Wei

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Datasets Mentioned

BETA
GM-CSF

Methods Mentioned

BETA
flow cytometry
lavage
ELISA
PCR

Software Mentioned

CFX96
Prism
FlowJo

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