NK Cells Control Tumor-Promoting Function of Neutrophils in Mice

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

doi:10.1158/2326-6066.cir-17-0204

Cited by 42 publications

(34 citation statements)

References 53 publications

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“…Crosstalk between neutrophils and NK cells has been suggested before in some conditions in humans and mice (12)(13)(14)(15). Recently, a link between neutrophils and NK cells in cancer has been described whereby neutrophils acquire a pro-tumour phenotype when NK cells are depleted (16). Intriguingly, in a model of experimental myocardial infarction, NK cell depletion resulted in increased neutrophilic pathology in the lungs of mice, raising the question of how this influence is mediated (17).…”

Section: Introductionmentioning

confidence: 99%

Pulmonary natural killer cells control neutrophil intravascular motility and response to acute inflammation

Secklehner

Filippo

Mackey

et al. 2019

Preprint

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The pulmonary immune system defends a huge surface area directly in contact with the contents of the air we breathe. Neutrophils, the most abundant immune cell in the pulmonary vasculature, are critical to immunity but they are also capable of generating life-threatening pathology. Natural Killer cells are the most highly represented lymphocyte subset in the lung, but relatively little is known about their localization, motility or the specific mechanisms by which they contribute to local homeostasis. Here, we used lung-intravital microscopy to directly visualise and quantify neutrophil and natural killer cell dynamics in the pulmonary vasculature of live mice. This approach revealed unexpected sessile behaviour by intravascular natural killer cells. Interactions with natural killer cells made neutrophils scan the endothelium more slowly over larger distances and reduced the number of neutrophils that accumulated in an LPS-triggered inflammatory challenge. This represents a new paradigm by which natural killer cells contribute to lung physiology by diminishing potentially pathogenic neutrophil accumulation.

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Section: Introductionmentioning

confidence: 99%

Pulmonary natural killer cells control neutrophil intravascular motility and response to acute inflammation

Secklehner

Filippo

Mackey

et al. 2019

Preprint

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“…In mice, CD27 hi NK cells (either Mac‐1 hi or Mac‐1 lo ), but not CD27 lo NK cells, are known to express CXCR3 and migrate to its ligands . In contrast to the findings of subcutaneous tumors, CXCR3 did not show any significant role in controlling tumor growth in lung. Moreover, blocking of the S1P pathway by treatment with FTY720 did not affect NK cell‐dependent tumor control in lung, although S1P5‐dependent NK cell trafficking was shown to be resistant to FTY720, suggesting NK cell recruitment through either a CXCR3 or a S1P pathway is not involved in pulmonary tumor control.…”

Section: Discussionmentioning

confidence: 65%

Lung‐resident natural killer cells control pulmonary tumor growth in mice

et al. 2018

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Accumulating evidence indicates the importance of natural killer (NK) cells in controlling tumor growth and metastasis. NK cell subsets display diversities in their function and tissue distribution and Mac‐1hi CD27lo NK cells are the predominant population of lung‐resident NK cells. Although the lung is a major organ where primary tumor develops and cancer cells metastasize, there is no clear evidence whether circulating NK cells and/or tissue‐resident NK cells control tumor growth in the lung. In the present study, we examined an antitumor function of lung‐resident NK cells to control pulmonary tumor growth. In an orthotopic lung tumor model, NK cells controlled pulmonary tumor growth, and mature circulating NK cell subsets were increased in tumor‐bearing lungs through a C‐X‐C motif chemokine receptor 3 (CXCR3)‐dependent mechanism. Although such increase in migratory NK cell subsets can be blocked by anti‐CXCR3 treatment, there was no difference in pulmonary tumor growth in anti‐CXCR3‐treated mice compared with control mice. In addition to pulmonary tumor growth, lung‐resident NK cells, but not migratory NK cells, play a dominant role in controlling metastatic growth of cancer cells in lung. These results strongly indicate an importance of lung‐resident NK cells for controlling pulmonary tumor growth.

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“…In the context of cancer, it was recently reported in a sarcoma transplantable model that NK cells regulated neutrophil functions via IFNγ. Upon NK cell depletion, neutrophils produced increased levels of VEGF‐A, therefore promoting angiogenesis and tumour progression …”

Section: Nk Cells and Neutrophilsmentioning

confidence: 99%

“…Upon NK cell depletion, neutrophils produced increased levels of VEGF-A, therefore promoting angiogenesis and tumour progression. 108…”

Section: Nk Cells and Neutrophilsmentioning

confidence: 99%

The yin‐yang of the interaction between myelomonocytic cells and NK cells

et al. 2018

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NK cells are innate lymphoid cells, which play a key role in the immune response to cancer and pathogens and participate in the shaping of adaptive immunity. NK cells engage in a complex bidirectional interaction with myelomonocytic cells. In particular, macrophages, dendritic cells and neutrophils promote differentiation and effector function of NK cells and, on the other hand, myelomonocytic cells express triggers of checkpoint blockade (eg PD-L1) and other immunosuppressive molecules, which negatively regulate NK cell function. In addition, NK cells express high levels of IL-1R8, which acts as a checkpoint for IL-18 driven differentiation and activation of NK cells. Evidence suggests that targeting the myeloid cell-NK cell crosstalk unleashes effective anti-tumour and anti-viral resistance.

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NK Cells Control Tumor-Promoting Function of Neutrophils in Mice

Cited by 42 publications

References 53 publications

Pulmonary natural killer cells control neutrophil intravascular motility and response to acute inflammation

Pulmonary natural killer cells control neutrophil intravascular motility and response to acute inflammation

Lung‐resident natural killer cells control pulmonary tumor growth in mice

The yin‐yang of the interaction between myelomonocytic cells and NK cells

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