NK cells control tumor-promoting function of neutrophils in mice

Keisuke Ogura, Marimo Sato-Matsushita, Seiji Yamamoto, Takashi Hori, Masakiyo Sasahara, Yoichiro Iwakura, Ikuo Saiki, Hideaki Tahara, Yoshihiro Hayakawa*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

Although natural killer (NK) cells are recognized as direct antitumor effectors, the ability of NK cells to control cancer-associated inflammation, which facilitates tumor progression, remains unknown. In this study, we demonstrate that NK cells control tumor-promoting inflammation through functional modificationofneutrophils.NKcellscontrolthetumor-promoting function of neutrophils through an IFNg-dependent mechanism. TumorprogressioninanNKcell–depletedhostisdiminishedwhen the IL17A–neutrophil axis is absent. In NK cell–depleted mice, neutrophils acquire a tumor-promoting phenotype, characterized by upregulation of VEGF-A expression, which promotes tumor growth and angiogenesis. A VEGFR inhibitor which preferentially suppressed tumor growth in NK cell–depleted mice was dependent on neutrophils. Furthermore, the systemic neutropenia caused by an antimetabolite treatment showed an anticancer effect only in mice lacking NK cells. Thus, NK cells likely control the tumor-promoting and angiogenic function of neutrophils.

Original languageEnglish
Pages (from-to)348-357
Number of pages10
JournalCancer Immunology Research
Volume6
Issue number3
DOIs
StatePublished - 2018/03/01

ASJC Scopus subject areas

  • General Medicine

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