Tumor-Associated Neutrophils in Cancer: Going Pro
Abstract
:1. Introduction
2. Neutrophil Recruitment in Cancer
3. Polarization States of Neutrophils in Cancer
4. Functions of Neutrophils in the Tumor Microenvironment
4.1. The Pro-Cancer Role of Neutrophils
4.1.1. Neutrophil Released Reactive Oxygen Species
4.1.2. Pro-Tumor Neutrophil-Secreted Cytokines and Chemokines
4.1.3. Neutrophil Released Enzymes
4.1.4. NET
4.1.5. Neutrophil and Therapy Resistance
4.2. The Anti-Cancer Role of Neutrophils
5. The Clinical Significance of Neutrophils
5.1. Neutrophils as A Potential Biomarker for Cancer Patients
5.2. Targeting Neutrophils in Cancer: The Therapeutic Plan
6. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Cancer Type | Cytokine/Chemokine | Stimulator | Target Cell | Effect | Reference |
---|---|---|---|---|---|
Breast cancer | Oncostatin M | GM-CSF signals. (cell-cell contact needed.) | Breast cancer cells | Induces vascular endothelial growth factor expression, cell detachment, and increases invasive potential. | [65] |
Adenocarcinoma of the bronchioloalveolar carcinoma (BAC) subtype | HGF | GM-CSF TNFα | BCA tumor cells | Promotes migration of tumor cells and is also positively associated with poorer outcome in BAC patients. An independent predictor of clinical outcome in multivariate analysis. | [66] |
Pancreatic cancer | TGF-β | Not shown | Not shown | Results in overproduction of collagens in pancreatic cancer, which ends in desmoplastic reaction. | [67] |
Head and neck cancer | CCL4 and CXCL8 | P38-MAPK | Not shown | Pro-tumor chemokine | [68] |
Gastric cancer | IL17 | TAM derived IL-6 and IL-23 | Neutrophils | Pro-inflammatory IL17 is a critical mediator of the recruitment of neutrophils into the invasive margin by CXC chemokines. | [39] |
Lung Adenocarcinoma | BV8 (Prok2) | G-CSF GM-CSF | Neutrophil | Promotes neutrophil chemotaxis. | [69] |
Thyroid cancer | CXCL8, VEGF-A, and TNF-α | Unknown | Not shown | Pro-inflammatory and angiogenic mediators. | [70] |
Hepatocellular carcinoma | CCL2, CCL3 | Unknown | Immune cells in the tumor microenvironment | The survival rate of the CCL2 high group was significantly lower than other patients. Host immune suppression. | [71] |
Oral cavity cancer | VEGF, IL-18 | Unknown | Not shown | May promote neoangiogenesis and metastatic cancer in the early stage of oral cavity cancer. | [72] |
Bladder cancer | CCL2, CCL3, CCL4, G-CSF, and IL-6 | Unknown | Not shown | Pro-inflammatory cytokine and chemokines. | [73] |
Cancer Type | Cytokine/Chemokine | Stimulator | Target Cell | Effect | Reference |
---|---|---|---|---|---|
Melanoma | VEGF | Not shown | Not shown | Promotes angiogenesis, tumor metastasis. | [74] |
Colitis-associated cancer | (IL)-1β (expression also seen in human neutrophils) | Not shown | Intestinal mononuclear phagocytes upregulate IL 6. | Induces tumor formation. | [75] |
Colon cancer | IL10 | Not shown | Regulates STAT3 activation to upregulate DNMT3b to silence tumor suppressor IRF8 in colonic epithelial cells. | Facilitates colon cancer initiation. | [76] |
Mesothelioma and lung carcinoma | CCL17 (expression also seen in human neutrophils) | Not shown | Regulatory T-cells | Facilitates the recruitment of regulatory T cells, which results in an immuno-suppressive nature. | [77] |
Breast cancer (Gr-1+CD11b+ immature myeloid cells) | CCL9 | TGF-β signaling | Myeloid cells | Promotes tumor cell survival in the pre-metastatic organ. | [78] |
Breast cancer | Prokineticin 2 (Prok2) | Not shown | Tumor cells | Enhances tumor cell proliferation. | [79] |
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Wu, L.; Saxena, S.; Awaji, M.; Singh, R.K. Tumor-Associated Neutrophils in Cancer: Going Pro. Cancers 2019, 11, 564. https://doi.org/10.3390/cancers11040564
Wu L, Saxena S, Awaji M, Singh RK. Tumor-Associated Neutrophils in Cancer: Going Pro. Cancers. 2019; 11(4):564. https://doi.org/10.3390/cancers11040564
Chicago/Turabian StyleWu, Lingyun, Sugandha Saxena, Mohammad Awaji, and Rakesh K. Singh. 2019. "Tumor-Associated Neutrophils in Cancer: Going Pro" Cancers 11, no. 4: 564. https://doi.org/10.3390/cancers11040564