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Abstract
<p class="first" id="d3186961e59">In recent years, the role of neutrophils in cancer
biology has been a matter of increasing
interest. Many patients with advanced cancer show high levels of neutrophilia, tumor
neutrophils are connected to dismal prognosis, and the neutrophil-to-lymphocyte ratio
has been introduced as a significant prognostic factor for survival in many types
of cancer. Neutrophils constitute an important portion of the infiltrating immune
cells in the tumor microenvironment, but controversy has long surrounded the function
of these cells in the context of cancer. Multiple evidences have shown that neutrophils
recruited to the tumor can acquire either protumor or antitumor function. These findings
have led to the identification of multiple and heterogeneous neutrophil subsets in
the tumor and circulation. In addition, tumor-associated neutrophils (TANs) were shown
to demonstrate functional plasticity, driven by multiple factors present in the tumor
microenvironment. In this review, we examine the current knowledge on cancer-related
circulating neutrophils, their source and the function of the different subtypes,
both mature and immature. We then discuss the pro vs antitumor nature of TANs in cancer,
their functional plasticity and the mechanisms that regulate neutrophil recruitment
and polarization. Although the vast majority of the knowledge on neutrophils in cancer
comes from murine studies, recent work has been done on human cancer-related neutrophils.
In the final paragraphs, we expand on the current knowledge regarding the role of
neutrophils in human cancer and examine the question whether cancer-related neutrophils
(circulating or intratumoral) could be a new possible target for cancer immunotherapy.
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