The Neutrophil: The Underdog That Packs a Punch in the Fight against Cancer

Abstract

The advent of immunotherapy has had a major impact on the outcome and overall survival in many types of cancer. Current immunotherapeutic strategies typically aim to (re)activate anticancer T cell immunity, although the targeting of macrophage-mediated anticancer innate immunity has also emerged in recent years. Neutrophils, although comprising ≈ 60% of all white blood cells in the circulation, are still largely overlooked in this respect. Nevertheless, neutrophils have evident anticancer activity and can induce phagocytosis, trogocytosis, as well as the direct cytotoxic elimination of cancer cells. Furthermore, therapeutic tumor-targeting monoclonal antibodies trigger anticancer immune responses through all innate Fc-receptor expressing cells, including neutrophils. Indeed, the depletion of neutrophils strongly reduced the efficacy of monoclonal antibody treatment and increased tumor progression in various preclinical studies. In addition, the infusion of neutrophils in murine cancer models reduced tumor progression. However, evidence on the anticancer effects of neutrophils is fragmentary and mostly obtained in in vitro assays or murine models with reports on anticancer neutrophil activity in humans lagging behind. In this review, we aim to give an overview of the available knowledge of anticancer activity by neutrophils. Furthermore, we will describe strategies being explored for the therapeutic activation of anticancer neutrophil activity.

Neutrophil extracellular traps participate in the development of cancer-associated thrombosis in patients with gastric cancer

“…Inflammation is one of the hallmarks of cancer. Additionally, neutrophils are among the most important immune cells implicated in promoting tumor progression[ 40 , 41 ]. NETs participate in cancer progression by promoting the proliferation, invasion, metastasis and angiogenesis of cancer cells as well as thrombosis in numerous tumor types[ 42 - 44 ].…”

SPP1 is a biomarker of cervical cancer prognosis and involved in immune infiltration

“…Tumor infiltrating dendritic cells tend to drive tumour progression through elevating the immunosuppression and tolerance (18). Infiltrating neutrophils play pro-tumoral functions by N2-subtype polarization (19). Here, high SPP1 indicated less CD8+ T cell and B cell tumor infiltration, whereas more infiltrated neutrophils, macrophages, and myeloid dendritic cells were correlated with high SPP1 expression.…”

Trogocytosis between Non-Immune Cells for Cell Clearance, and among Immune-Related Cells for Modulating Immune Responses and Autoimmunity

“…Besides, Treffers et al [ 108 ] even disclosed that IgA antibodies were superior to IgG antibodies in killing cancer cells by PMN in combination with CD47-SIRPα checkpoint inhibitor. A comprehensive review of neutrophils in fighting against cancers has been reported by Usyannovska Avtenyuk et al [ 109 ].…”