Journal
AMERICAN JOURNAL OF SURGERY
Volume 214, Issue 5, Pages 938-944Publisher
EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
DOI: 10.1016/j.amjsurg.2017.08.003
Keywords
Tumor microenvironment; Immunomodulation; Tumor progression; Metastasis; Cytokines; Chemokines; Metastasis; Tumor-associated neutrophils
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Importance: Neutrophils have classically been considered to mount a defensive response against tumor cells, yet recent evidence suggests tumors modulate neutrophil function to support tumor growth and progression. Observations: Tumor-associated neutrophils (TANs) are phenotypically distinct from circulating neutrophils in terms of their surface protein composition and cyto/chemokine activity and response. Although TANs have been shown to both promote and inhibit tumor advancement, the preponderant activity augments tumor progression. This review discusses these cancer-promoting molecular pathways, relevant diagnostic studies in patients, and subsequent treatment modalities. The tumor promoting mechanisms of TANs include dampening of CD8(+) response via Arginase-1; a neutrophil-secreted neutrophil elastase (NE) upregulation of tumor cellular proliferation pathways; degradation of basement membrane and ECM via NE and MMP-9; upregulation of angiogenesis by VEGF, and HGF; and ICAM-1 dependent tumor intravasation, immune protection in circulation, and extravasation into distant, metastatic tissue beds. Clinicians are constrained in treating TANs systemically as it may induce neutropenia, therefore targeting TANs-mediated tumor progression pathways surgically on a loco-regional level is a viable adjuvant treatment modality. Conclusion and relevance: TANs modulate the tumor microenvironment promoting tumor progression. Mechanistic understanding of TANs role in tumor progression will provide unique therapeutic alternatives. Published by Elsevier Inc.
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