Abstract
Neutrophils are essential to combat infectious agents but contribute to collateral inflammatory damage. Likewise, neutrophils can kill cancer cells and have been shown to promote malignant growth and metastasis through immunosuppressive functions. Two articles in a recent issue of Nature reveal new mechanisms by which tumors induce changes in neutrophil phenotype through production of inflammatory cytokines. Although the two studies report different outcomes on the effects of neutrophils on tumor growth and metastasis, they delineate novel molecular pathways influencing neutrophil phenotype that may provide new approaches to harnessing neutrophil functions in the treatment of cancer.
Highlights
Neutrophils are essential to combat infectious agents but contribute to collateral inflammatory damage
In the first highlighted article, Finisguerra et al investigated the function of the MET proto-oncogene in stromal cells, including leukocytes associated with tumors [2]. They convincingly demonstrated that deletion of MET in neutrophils was associated with increased tumor growth and metastasis in multiple tumor models in mice, including spontaneous mammary tumors driven by transgenic expression of the polyoma virus middle T (PyMT) antigen
Tumor necrosis factor-alpha (TNF-α) and other soluble factors produced by tumor cells were responsible for Met induction in a subset of circulating neutrophils of tumor-bearing mice, and the Met+ neutrophil subset was enriched within the tumor mass and contributed to reduced tumor growth and metastasis
Summary
Neutrophils are essential to combat infectious agents but contribute to collateral inflammatory damage. In cancer patients and tumor-bearing mice, a major question has been the elusive origin and functional characterization of tumor-associated neutrophils and granulocytic myeloidderived suppressor cells (G-MDSCs), which can be considered a subset of neutrophils with immunosuppressive activity on T cells. In two recent studies published in Nature [2, 3], tumor-induced mechanisms were shown to alter neutrophil numbers and function, highlighting the plasticity of the neutrophil and its importance in controlling growth and invasiveness of cancer cells.
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