The Complex Role of Neutrophils in Tumor Angiogenesis and Metastasis

Abstract

Chronic inflammation fosters cancer development and progression and also modulates tumor responses to anticancer therapies. Neutrophils are key effector cells in innate immunity and are known to play a critical role in various inflammatory disorders. However, the functions of neutrophils in cancer pathogenesis have been largely neglected until recently and still remain poorly characterized compared with other immune cells in the tumor microenvironment. We highlight recent findings on the mechanisms by which tumor cells, in cooperation with tumorassociated stromal cells, induce expansion, recruitment, and polarization of neutrophils. We also review the multifaceted roles that neutrophils play in different aspects of cancer development and progression, with an emphasis on tumor angiogenesis and metastasis.

Interleukin-17–Producing Neutrophils Link Inflammatory Stimuli to Disease Progression by Promoting Angiogenesis in Gastric Cancer

“…These findings are consistent with the general view that the tumor microenvironment promotes tumor progression by stimulating angiogenesis and tissue remodeling. Gaps remain in our understanding of neutrophil plasticity and the switch between pro-and antitumor effects (5,7,34). The present study demonstrates that IL17 þ neutrophils are a critical mediator of the recruitment of neutrophils to gastric cancer cells based on the following findings.…”

The Interplay Between Neutrophils and CD8+ T Cells Improves Survival in Human Colorectal Cancer

“…The fact that in a variety of tumors other than colorectal cancer, neutrophil infiltration has been suggested to be associated with poor prognosis (35,43,44) raises the issue of the specificities inherent in neutrophil infiltration in colorectal cancer. The (24) appear to contradict our results.…”

The ever-expanding role of HIF in tumour and stromal biology

“…Hypoxia prolongs neutrophil survival, and HIF-dependent increases in glycolytic metabolism are important for neutrophil function in hypoxia 118,133 . Similar to macrophages, neutrophil function can be classified into N1 and N2 polarization, with N2 neutrophils displaying tumour promoting properties analogous to the role of M2 macrophages in tumour progression 134 . TGF-β in the tumour microenvironment promotes N2 neutrophil polarization, thereby enhancing their tumour promoting function 135 .…”