Table 2 Neutrophil roles in carcinogenesis, cancer growth and metastasis
Cancer | Year | Species | Mechanism | References |
|---|---|---|---|---|
Cancer-promoting role | ||||
Lung cancer | 2010 | Mouse | Neutrophil elastase accelerates lung cancer growth via degradation of IRS-1 | [138] |
Lung carcinoma, melanoma | 2016 | Mouse | NETosis promotes cancer growth | [139] |
Small intestinal cancer | 2016 | Mouse | Hypercoagulation induced by NETosis promotes carcinogenesis and N2 polarization | [140] |
Lung adenocarcinoma | 2017 | Human, mouse | A distinct subset of SiglecFhigh neutrophils dependent on cancer-induced osteoblastic cells promote cancer growth | [141] |
Melanoma | 2017 | Mouse | Neutrophils recruit to TME and acquire immunosuppressive properties | [142] |
Lymphoma, Lung carcinoma, colon carcinoma, pancreatic cancer | 2019 | Mouse | Neutrophils acquire immunosuppressive activity mediated by FATP2 | [143] |
Lung adenocarcinoma | 2020 | Human | Multi-omics reveal a potential immunosuppressive role of neutrophil degranulation | [144] |
Hepatocellular carcinoma | 2011 | Human | Neutrophil is correlated with angiogenesis progression | [145] |
Pancreatic cancer | 2016 | Mouse | CXCR2 signaling promotes carcinogenesis and metastasis | [146] |
Lung carcinoma | 2013 | Mouse | NETs trap circulating cancer cells and promote metastasis | [121] |
Breast cancer | 2015 | Mouse | Neutrophil-derived leukotrienes establish the lung pre-metastatic niche | [126] |
Breast cancer | 2015 | Mouse | Neutrophils polarized by IL-17-producing γδ T cells acquire the ability to suppress cytotoxic T lymphocytes and promotes metastasis | [113] |
Lung carcinoma, melanoma | 2016 | Mouse | Neutrophils recruited by TLR3 promote lung pre-metastatic niche formation | [127] |
Breast cancer | 2016 | Mouse | NETs induced by cancer promote metastasis | [147] |
Breast cancer | 2018 | Mouse | NETs produced during inflammation awaken dormant cancer cells | [72] |
Breast cancer | 2019 | Mouse | WNT-dependent systemic neutrophilic inflammation triggered by loss of p53 in cancer cells promotes metastasis | [148] |
Breast cancer | 2019 | Human, mouse | Neutrophils escorting CTCs drives cell cycle progression and expands the metastatic potential of CTCs | [123] |
Breast cancer, colon cancer | 2020 | Human | NETs promote metastasis via binding CCDC25 on cancer cells | [149] |
Cancer-suppressing role | ||||
Breast cancer | 2011 | Mouse | Neutrophils inhibit lung metastasis by generating H2O2 | [130] |
Lung cancer | 2014 | Human | TANs stimulate T cell responses in the early stage of lung cancer | [150] |
Uterine cancer | 2015 | Mouse | Neutrophils oppose carcinogenesis via clearance of hypoxic cancer cells | [151] |
Lung cancer | 2016 | Human | TANs act as APCs in early-stage lung cancer | [152] |
Colorectal cancer | 2017 | Human | Neutrophils enhance the responsiveness of CD8+ T cells and improve survival | [153] |
Undifferentiated pleomorphic sarcoma (UPS) | 2019 | Human | Neutrophils driving UTCαβ polarization and type 1 immunity mediate resistance against UPS | [154] |
Uterine cancer | 2020 | Mouse | Neutrophils kill cancer cells via their production of ROS and MMP-9 upon relief of hypoxia | [155] |
35 cancer cell lines | 2021 | Human | Neutrophil elastase selectively kills cancer cells and attenuates carcinogenesis | [70] |
Neutrophil-associated complications in cancer | ||||
Mammary carcinoma | 2015 | Mouse | Kidney and heart failure caused by NETosis and inflammation | [156] |
Lung carcinoma | 2015 | Mouse | HGF/MET-dependent neutrophil recruitment and NO release by neutrophils promotes cancer cell killing | [105] |
Small intestinal cancer | 2016 | Mouse | Coagulation promoted by NETosis | [140] |
Myeloproliferative neoplasm | 2018 | Mouse | Thrombosis promoted by increased NETosis | [157] |
Neutrophils with anticancer therapeutic role | ||||
Non-Hodgkin lymphoma | 2010 | Mouse | Neutrophils kill cancer cells by phagocytosis in the treatment of anti-CD47 antibodies synergized with rituximab | [158] |
Thymoma, breast cancer | 2010 2014 | Mouse | MDSCs are selectively killed by 5-Fluorouracil or doxorubicin selectively resulting in enhanced T cell-dependent anticancer immunity | |
Different cancer cell lines | 2013 | Mouse | 5-FU and gemcitabine can promote cancer inflammation and resistance to chemotherapy mediated by neutrophils and T cells | [161] |
Different cancer cell lines | 2016 | Mouse | Radiotherapy induces infiltration of neutrophils with cytotoxic activity against cancer cells | [162] |
Glioma | 2017 | Mouse | Neutrophil can act as a vector of anticancer drug delivery to cross BBB for suppression of postoperative malignant cancer recurrence | [163] |
Different cancer cell lines | 2018 | Mouse | Neutrophils kill antibody-opsonized cancer cells by trogoptosis | [107] |
Lung carcinoma | 2018 | Mouse | TANs are reprogrammed to promote anticancer immunity by blocking LILRB2 | [164] |
Different cancer cell lines | 2020 | Mouse | Neutrophils kill cancer cells via ADCC mediated by IgA and enhanced by CD47–SIRPα checkpoint inhibition | [165] |