. 2021 Sep 20;10(9):2486. doi: 10.3390/cells10092486

Table 1.

Examples of tumor models showing pro-tumor neutrophil functions.

Tumor Source	Effect of Neutrophil Elimination	Reference
UV-light induced cancer 4102-PRO that has become resistant to cytotoxic T cells	Elimination of the neutrophils with anti-granulocyte antibodies reduced tumor growth.	[50]
RT7-4bs rat hepatocarcinoma cells	Neutrophils facilitate the attachment of the hepatocarcinoma cells to vascular endothelial cells and increase tumor cell retention in the lungs.	[52]
QR-32 fibrosarcoma	Neutrophil depletion prevented lung metastasis formation without affecting the primary tumor. When conducting the experiment in integrin β2 KO mice that had impaired infiltration of neutrophils into the tumor, a strong reduction in lung metastasis was observed.	[51]
66c14 breast carcinoma cells	Elimination of neutrophils reduced the number of metastases.	[77]
B16F10 melanoma and MCA205 fibrosarcoma cells	Depletion of neutrophils inhibited tumor growth.	[53]
H-59 Lewis lung carcinoma cells	Neutrophil depletion reduced the development of surface liver metastases.	[54]
Chronic colitis-induced colon cancer	Depletion of neutrophils after the last administration of dextran sulfate sodium (DSS), reduced the number and size of the tumors, concomitant with decreased expression of CXCL2, Matrix metalloproteinase 9 and Neutrophil elastase.	[55]
MMTV-PyMT mammary tumor model	Depletion of neutrophils in Rag1-null immune-comprised mice harboring primary tumors during the pre-metastatic stage, led to decreased metastatic seeding.	[76]
A model of invasive intestinal adenocarcinoma (AhCreER; Apc^fl/+; Pten^fl/fl mice).	Depletion of neutrophils suppressed DMBA/TPA-induced skin tumor growth and colitis-associated intestinal tumorigenesis and reduced Apc^Min/+ adenoma formation.	[78]
A spontaneous breast cancer model (K14^cre; Cdh1^F/F; Trp53^F/F; KEP) mice	IL-17 produced by tumor-infiltrating γδ T cells recruits, expands and activate neutrophils to promote lung metastasis of breast cancer. Neutrophil depletion resulted in significant reduction in both pulmonary and lymph node metastasis without affecting the primary tumor growth.	[71]
LPS-induced lung inflammation model for metastatic seeding of B16-BL6 melanoma and LLC Lewis lung carcinoma cells	Recruitment of neutrophils expressing the inflammatory mediators IL-1β, TNFα, IL-6 and COX2. Depletion of neutrophils suppressed LLC lung metastases. Neutrophil elastase and Cathepsin G degrade Thrombospondin 1, thereby facilitate metastatic seeding in the lung. Mice transplanted with neutrophils deficient for Neutrophil elastase and Cathepsin G showed defective lung metastasis of LLC.	[79]
4T1 subclones selected for high metastasis to the liver, the bone marrow, or the lung	Depletion of neutrophils reduced the liver metastatic burden, but not bone or lung metastatic burdens.	[80]
MMTV-PyVT spontaneous breast cancer model in Col1a1^tm1Jae mice resulting in collagen-dense tumors	GM-CSF levels were increased in collagen-dense tumors. Depletion of neutrophils reduced the number of tumors and blocked metastasis in more than 80% of mice with collagen-dense tumors but had no effect on tumor growth or metastasis in wild-type mice.	[57]
Kras^G12D-driven mouse model of lung cancer	Depletion of Gr1⁺ cells reduced lung tumor growth, reverted immune exclusion and sensitized lesions to anti-PD1 immunotherapy.	[81]
Human HCT-116, LoVo and HT29 colon carcinoma cells	Human colorectal cancer liver metastases and murine gastrointestinal experimental liver metastases are infiltrated by neutrophils. Depletion of neutrophils in established experimental, murine liver metastases led to diminished metastatic growth. Neutrophils contribute to angiogenesis through secretion of FGF2.	[82]
IL-11⁺ and VEGFD⁺ subclones of human MDA-MB-468 breast cancer cells	Depletion of neutrophils prevents lung metastasis without affecting the primary tumor growth. The chemoattractants CXCL12, CXCL14 and CXCL1 that promote the pro-tumor neutrophil phenotype, were found to be secreted by IL-11-responsive mesenchymal stromal cells in the tumor microenvironment.	[58]
Chemically induced cutaneous squamous cell carcinoma (cSCC)	Depletion of neutrophils delayed tumor growth and significantly increased the frequency of proliferating IFNγ-producing CD8⁺ T cells.	[59]
Chronic wound inflammation-induced melanoma in Ras^G12V zebrafish larvae	Delaying the development of neutrophils using morpholinos to G-CSF, reduced the number of premetastatic cells.	[56]