NK cells control tumor-promoting function of neutrophils in mice.

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NK cells control tumor-promoting function of neutrophils in mice.

Cancer Immunol Res. 2018 Jan 23;:

Authors: Ogura K, Sato-Matsushita M, Yamamoto S, Hori T, Sasahara M, Iwakura Y, Saiki I, Tahara H, Hayakawa Y

Abstract
Although 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 modification of neutrophils. NK cells control the tumor-promoting function of neutrophils through an IFNgamma-dependent mechanism. Tumor progression in an NK cell-depleted host is diminished when the IL17A-neutrophil axis is absent. In NK cell-depleted mice, neutrophils acquire a tumor-promoting phenotype, characterized by up-regulation 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 anti-metabolite treatment showed an anti-cancer effect only in mice lacking NK cells. Thus, NK cells likely control the tumor-promoting and angiogenic function of neutrophils.

PMID: 29362222 [PubMed - as supplied by publisher]

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