Neutrophils as myeloid‐derived suppressor cells

Abstract

Neutrophils form the first line of defence against invading pathogens, such as bacteria and fungi, as part of the innate immune response. Recently, neutrophils have also been discovered as repressors of adaptive immune responses. Under certain conditions, such as cancer and severe injury, an expansion of immature and mature neutrophils has been observed to induce suppression of T-cell proliferation. These suppressing cells are known as so-called myeloid-derived suppressor cells (MDSCs), a heterogeneous population of granulocytic-MDSCs and monocytic-MDSCs. Initially, MDSCs were believed to be a specific immature type of myeloid immune cell released from the bone marrow, but mature neutrophils have also been proposed to have suppressive capacity. However, granulocytic-MDSCs show a similar morphology and expression of cell surface markers as mature neutrophils. The only characteristic that discriminates granulocytic (g)-MDSCs from mature neutrophils is their suppressive capacity, raising the question whether human g-MDSCs and neutrophils are actually different cell types or whether they are one plastic cell type that can functionally polarize from microbial killers to immunosuppressor cells, depending on local conditions. In this review, we will focus on the MDSC activity of circulating mature neutrophils.

Dynamics of blood neutrophil‐related indices during nivolumab treatment may be associated with response to salvage chemotherapy for non‐small cell lung cancer: A hypothesis‐generating study

“…More recent studies have shown that an early decrease in NLR during treatment with PD‐1 inhibitors predicts its efficacy . NLR and ANC have been reported to correlate with the number of circulating MDSCs and tumor‐associated neutrophils, which suppress the function of antitumor T cells . Circulating MDSC levels were inversely associated with response rate and survival after treatment with nivolumab in cancer patients .…”

“…Several studies have shown that the neutrophil‐to‐lymphocyte ratio (NLR) and the absolute neutrophil count (ANC) in the blood can predict the efficacy of PD‐1 inhibitors in patients with NSCLC . NLR and ANC have also been reported to reflect the number of circulating myeloid‐derived suppressor cells (MDSCs) and tumor‐associated neutrophils, which inhibit the function of antitumor T cells . The immunosuppressive status in the tumor microenvironment could be monitored using the dynamics of NLR and ANC.…”

“…5-10 NLR and ANC have also been reported to reflect the number of circulating myeloid-derived suppressor cells (MDSCs) and tumor-associated neutrophils, [11][12][13][14][15] which inhibit the function of antitumor T cells. 16,17 The immunosuppressive status in the tumor microenvironment could be monitored using the dynamics of NLR and ANC. Thus, the time-series patterns of NLR and ANC during nivolumab treatment were retrospectively explored in lung cancer patients who received subsequent salvage chemotherapy to find an immunological clue to design future studies.…”

Therapeutic targeting of neutrophil exocytosis

“…The regulation of the innate and adaptive immune systems by neutrophils has been reviewed extensively . Neutrophil granule contents participate in many regulatory activities, including those involving T cells, dendritic cells, B cells, and monocytes .…”

“…The regulation of the innate and adaptive immune systems by neutrophils has been reviewed extensively. [70][71][72][73][74][75][76][77][78][79] Neutrophil granule contents participate in many regulatory activities, including those involving T cells, dendritic cells, B cells, and monocytes. 70,72,73,80 The interaction between neutrophils and monocytes is particularly relevant to antimicrobial activity and inflammatory diseases.…”