Tumor-associated neutrophils suppress antitumor immunity of NK cells through the PD-L1/PD-1 axis

Translational Oncology
Rui SunJueping Feng

Abstract

Studies have begun to emerge showing the protumor effects of tumor-associated neutrophils (TANs) in tumorigenesis, which may involve dysfunction of NK cells. However, the mechanism through which these rebellious neutrophils modulate NK cell immunity in tumor-bearing state remains unclear. In the present study, we demonstrate that neutrophils can impair the cytotoxicity and infiltration capability of NK cells, and downregulate CCR1 resulting in the weakened infiltration capability of NK cells. Moreover, neutrophils can decrease the responsiveness of NK-activating receptors, NKp46 and NKG2D. Mechanistically, enhanced PD-L1 on neutrophils and PD-1 on NK cells, and subsequent PD-L1/PD-1 interactions were the main mechanisms determining the suppression of neutrophils in NK cell immunity. G-CSF/STAT3 pathway was responsible for PD-L1 upregulation on neutrophils, while IL-18 was essential for PD-1 enhancement on NK cells. The crosstalk between neutrophils and NK cells was cell-cell interaction-dependent. These findings suggest that neutrophils can suppress the antitumor immunity of NK cells in tumor-bearing status through the PD-L1/PD-1 axis, highlighting the importance of PD-L1/PD-1 in the inhibitory effect of neutrophils on NK cells...Continue Reading

Citations

Oct 28, 2020·International Journal of Molecular Sciences·Natasha Ustyanovska AvtenyukValerie R Wiersma
Oct 31, 2020·Cancers·Mireia BachillerBeatriz Martín-Antonio

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Methods Mentioned

BETA
chips
flow cytometry
fluorescence microscopy
ELISA
transfection

Software Mentioned

CellQuest
SPSS

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