Roles of neutrophils in cancer growth and progression

Journal of Leukocyte Biology

Volumn 103, Issue 3, 2018, Pages 457-464

  Galdiero, Maria Rosaria ^a   Varricchi, Gilda ^a   Loffredo, Stefania ^a   Mantovani, Alberto ^b,c   Marone, Gianni ^a,d  

^a UNIVERSITY OF NAPLES FEDERICO II   (Italy)

^b HUMANITAS CLINICAL AND RESEARCH CENTER   (Italy)

^c HUMANITAS UNIVERSITY   (Italy)

^d CNR   (Italy)

Author keywords

cancer immunotherapy; cancer related inflammation; predictive biomarker; prognostic factor; tumor associated neutrophils

Indexed keywords

ANTINEOPLASTIC AGENT; BIOLOGICAL MARKER;

ANTIANGIOGENIC ACTIVITY; CANCER GROWTH; CANCER PROGNOSIS; CELL FUNCTION; HUMAN; IMMUNOCOMPETENT CELL; INFLAMMATION; METASTASIS; NEUTROPHIL; NONHUMAN; PRIORITY JOURNAL; REVIEW; TREATMENT RESPONSE; TUMOR MICROENVIRONMENT; ANIMAL; DISEASE EXACERBATION; IMMUNOLOGY; NEOPLASM; PATHOLOGY;

ANIMALS; DISEASE PROGRESSION; HUMANS; INFLAMMATION; NEOPLASMS; NEUTROPHILS; TUMOR MICROENVIRONMENT;

EID: 85042549858     PISSN: 07415400     EISSN: 19383673     Source Type: Journal    
DOI: 10.1002/JLB.3MR0717-292R     Document Type: Review

References (98)

1. Dvorak HF. Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med. 1986;315(26):1650–1659.
2. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–674.
3. Biswas SK, Mantovani A. Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm. Nat Immunol. 2010;11(10):889–896.
4. Bonavita E, Galdiero MR, Jaillon S, Mantovani A. Phagocytes as corrupted policemen in cancer-related inflammation. Adv Cancer Res. 2015;128:141–171.
5. Galdiero MR, Bonavita E, Barajon I, Garlanda C, Mantovani A, Jaillon S. Tumor associated macrophages and neutrophils in cancer. Immunobiology. 2013;218(11):1402–1410.
6. Granot Z, Jablonska J. Distinct functions of neutrophil in cancer and its regulation. Mediators Inflamm. 2015;2015:701067.
7. Fridlender ZG, Sun J, Kim S, Kapoor V, Cheng G, Ling L, et al. Polarization of tumor-associated neutrophil phenotype by TGF-beta: “N1” versus “N2” TAN. Cancer Cell. 2009;16(3):183–194.
8. Mantovani A. The yin-yang of tumor-associated neutrophils. Cancer Cell. 2009;16(3):173–174.
9. Jablonska J, Leschner S, Westphal K, Lienenklaus S, Weiss S. Neutrophils responsive to endogenous IFN-beta regulate tumor angiogenesis and growth in a mouse tumor model. J Clin Invest. 2010;120(4):1151–1164.
10. Keeley EC, Mehrad B, Strieter RM. CXC chemokines in cancer angiogenesis and metastases. Adv Cancer Res. 2010;106:91–111.
11. Lazennec G, Richmond A. Chemokines and chemokine receptors: new insights into cancer-related inflammation. Trends Mol Med. 2010;16(3):133–144.
12. Mantovani A, Cassatella MA, Costantini C, Jaillon S. Neutrophils in the activation and regulation of innate and adaptive immunity. Nat Rev Immunol. 2011;11(8):519–531.
13. Dumitru CA, Gholaman H, Trellakis S, et al. Tumor-derived macrophage migration inhibitory factor modulates the biology of head and neck cancer cells via neutrophil activation. Int J Cancer. 2011;129(4):859–869.
14. Trellakis S, Farjah H, Bruderek K, et al. Peripheral blood neutrophil granulocytes from patients with head and neck squamous cell carcinoma functionally differ from their counterparts in healthy donors. Int J Immunopathol Pharmacol. 2011;24(3):683–693.
15. Kuang DM, Zhao Q, Wu Y, et al. Peritumoral neutrophils link inflammatory response to disease progression by fostering angiogenesis in hepatocellular carcinoma. J Hepatol. 2011;54(5):948–955.
16. Ijichi H, Chytil A, Gorska AE, et al. Inhibiting Cxcr2 disrupts tumor-stromal interactions and improves survival in a mouse model of pancreatic ductal adenocarcinoma. J Clin Invest. 2011;121(10):4106–4117.
17. Keane MP, Belperio JA, Xue YY, Burdick MD, Strieter RM. Depletion of CXCR2 inhibits tumor growth and angiogenesis in a murine model of lung cancer. J Immunol. 2004;172(5):2853–2860.
18. Jamieson T, Clarke M, Steele CW, et al. Inhibition of CXCR2 profoundly suppresses inflammation-driven and spontaneous tumorigenesis. J Clin Invest. 2012;122(9):3127–3144.
19. Matsui A, Yokoo H, Negishi Y, et al. CXCL17 expression by tumor cells recruits CD11b+Gr1 high F4/80- cells and promotes tumor progression. PLoS One. 2012;7(8):e44080.
20. Cortez-Retamozo V, Etzrodt M, Newton A, et al. Origins of tumor-associated macrophages and neutrophils. Proc Natl Acad Sci USA. 2012;109(7):2491–2496.
21. Gungor N, Knaapen AM, Munnia A, et al. Genotoxic effects of neutrophils and hypochlorous acid. Mutagenesis. 2010;25(2):149–154.
22. Houghton AM, Rzymkiewicz DM, Ji H, et al. Neutrophil elastase-mediated degradation of IRS-1 accelerates lung tumor growth. Nat Med. 2010;16(2):219–223.
23. Grosse-Steffen T, Giese T, Giese N, et al. Epithelial-to-mesenchymal transition in pancreatic ductal adenocarcinoma and pancreatic tumor cell lines: the role of neutrophils and neutrophil-derived elastase. Clin Dev Immunol. 2012;2012:720768.
24. Chawla A, Alatrash G, Philips AV, et al. Neutrophil elastase enhances antigen presentation by upregulating human leukocyte antigen class I expression on tumor cells. Cancer Immunol Immunother. 2016;65(6):741–751.
25. Mittendorf EA, Alatrash G, Qiao N, et al. Breast cancer cell uptake of the inflammatory mediator neutrophil elastase triggers an anticancer adaptive immune response. Cancer Res. 2012;72(13):3153–3162.
26. Queen MM, Ryan RE, Holzer RG, Keller-Peck CR, Jorcyk CL. Breast cancer cells stimulate neutrophils to produce oncostatin M: potential implications for tumor progression. Cancer Res. 2005;65(19):8896–8904.
27. Wislez M, Rabbe N, Marchal J, Milleron B, Crestani B, Mayaud C, et al. Hepatocyte growth factor production by neutrophils infiltrating bronchioloalveolar subtype pulmonary adenocarcinoma: role in tumor progression and death. Cancer Res. 2003;63(6):1405–1412.
28. Imai Y, Kubota Y, Yamamoto S, et al. Neutrophils enhance invasion activity of human cholangiocellular carcinoma and hepatocellular carcinoma cells: an in vitro study. J Gastroenterol Hepatol. 2005;20(2):287–293.
29. Cassatella MA. On the production of TNF-related apoptosis-inducing ligand (TRAIL/Apo-2L) by human neutrophils. J Leukoc Biol. 2006;79(6):1140–1149.
30. Hewish M, Lord CJ, Martin SA, Cunningham D, Ashworth A. Mismatch repair deficient colorectal cancer in the era of personalized treatment. Nat Rev Clin Oncol. 2010;7(4):197–208.
31. Kemp TJ, Ludwig AT, Earel JK, et al. Neutrophil stimulation with Mycobacterium bovis bacillus Calmette-Guerin (BCG) results in the release of functional soluble TRAIL/Apo-2L. Blood. 2005;106(10):3474–3482.
32. Tanaka H, Ito T, Kyo T, Kimura A. Treatment with IFNalpha in vivo up-regulates serum-soluble TNF-related apoptosis inducing ligand (sTRAIL) levels and TRAIL mRNA expressions in neutrophils in chronic myelogenous leukemia patients. Eur J Haematol. 2007;78(5):389–398.
33. Tecchio C, Huber V, Scapini P, et al. IFNalpha-stimulated neutrophils and monocytes release a soluble form of TNF-related apoptosis-inducing ligand (TRAIL/Apo-2 ligand) displaying apoptotic activity on leukemic cells. Blood. 2004;103(10):3837–3844.
34. Eruslanov EB, Bhojnagarwala PS, Quatromoni JG, et al. Tumor-associated neutrophils stimulate T cell responses in early-stage human lung cancer. J Clin Invest. 2014;124(12):5466–5480.
35. Blaisdell A, Crequer A, Columbus D, et al. Neutrophils oppose uterine epithelial carcinogenesis via debridement of hypoxic tumor cells. Cancer Cell. 2015;28(6):785–799.
36. Wu P, Wu D, Ni C, et al. gammadeltaT17 cells promote the accumulation and expansion of myeloid-derived suppressor cells in human colorectal cancer. Immunity. 2014;40(5):785–800.
37. Dumitru CA, Fechner MK, Hoffmann TK, Lang S, Brandau S. A novel p38-MAPK signaling axis modulates neutrophil biology in head and neck cancer. J Leukoc Biol. 2012;91(4):591–598.
38. Nozawa H, Chiu C, Hanahan D. Infiltrating neutrophils mediate the initial angiogenic switch in a mouse model of multistage carcinogenesis. Proc Natl Acad Sci USA. 2006;103(33):12493–12498.
39. Ardi VC, Kupriyanova TA, Deryugina EI, Quigley JP. Human neutrophils uniquely release TIMP-free MMP-9 to provide a potent catalytic stimulator of angiogenesis. Proc Natl Acad Sci USA. 2007;104(51):20262–20267.
40. Leifler KS, Svensson S, Abrahamsson A, et al. Inflammation induced by MMP-9 enhances tumor regression of experimental breast cancer. J Immunol. 2013;190(8):4420–4430.
41. Shojaei F, Wu X, Zhong C, et al. Bv8 regulates myeloid-cell-dependent tumour angiogenesis. Nature. 2007;450(7171):825–831.
42. Shojaei F, Singh M, Thompson JD, Ferrara N. Role of Bv8 in neutrophil-dependent angiogenesis in a transgenic model of cancer progression. Proc Natl Acad Sci USA. 2008;105(7):2640–2645.
43. Shojaei F, Wu X, Qu X, et al. G-CSF-initiated myeloid cell mobilization and angiogenesis mediate tumor refractoriness to anti-VEGF therapy in mouse models. Proc Natl Acad Sci USA. 2009;106(16):6742–6747.
44. Ai S, Cheng XW, Inoue A, et al. Angiogenic activity of bFGF and VEGF suppressed by proteolytic cleavage by neutrophil elastase. Biochem Biophys Res Commun. 2007;364(2):395–401.
45. Scapini P, Morini M, Tecchio C, et al. CXCL1/macrophage inflammatory protein-2-induced angiogenesis in vivo is mediated by neutrophil-derived vascular endothelial growth factor-A. J Immunol. 2004;172(8):5034–5040.
46. Loffredo S, Borriello F, Iannone R, et al. Group V secreted phospholipase A2 induces the release of proangiogenic and antiangiogenic factors by human neutrophils. Front Immunol. 2017;8:443.
47. Huh SJ, Liang S, Sharma A, Dong C, Robertson GP. Transiently entrapped circulating tumor cells interact with neutrophils to facilitate lung metastasis development. Cancer Res. 2010;70(14):6071–6082.
48. Cools-Lartigue J, Spicer J, McDonald B, et al. Neutrophil extracellular traps sequester circulating tumor cells and promote metastasis. J Clin Invest. 2013.
49. Granot Z, Henke E, Comen EA, King TA, Norton L, Benezra R. Tumor entrained neutrophils inhibit seeding in the premetastatic lung. Cancer Cell. 2011;20(3):300–314.
50. Akbay EA, Koyama S, Liu Y, et al. Interleukin-17A promotes lung tumor progression through neutrophil attraction to tumor sites and mediating resistance to PD-1 blockade. J Thorac Oncol. 2017;12:1268–1279.
51. Boyum A. Isolation of mononuclear cells and granulocytes from human blood. Isolation of monuclear cells by one centrifugation, and of granulocytes by combining centrifugation and sedimentation at 1 g. Scand J Clin Lab Invest Suppl. 1968;97:77–89.
52. Denny MF, Yalavarthi S, Zhao W, et al. A distinct subset of proinflammatory neutrophils isolated from patients with systemic lupus erythematosus induces vascular damage and synthesizes type I IFNs. J Immunol. 2010;184(6):3284–3297.
53. Cloke T, Munder M, Taylor G, Muller I, Kropf P. Characterization of a novel population of low-density granulocytes associated with disease severity in HIV-1 infection. PLoS One. 2012;7(11):e48939.
54. Rodriguez PC, Ernstoff MS, Hernandez C, et al. Arginase I-producing myeloid-derived suppressor cells in renal cell carcinoma are a subpopulation of activated granulocytes. Cancer Res. 2009;69(4):1553–1560.
55. Schmielau J, Finn OJ. Activated granulocytes and granulocyte-derived hydrogen peroxide are the underlying mechanism of suppression of t-cell function in advanced cancer patients. Cancer Res. 2001;61(12):4756–4760.
56. Mishalian I, Granot Z, Fridlender ZG. The diversity of circulating neutrophils in cancer. Immunobiology. 2017;222(1):82–88.
57. Peranzoni E, Zilio S, Marigo I, et al. Myeloid-derived suppressor cell heterogeneity and subset definition. Curr Opin Immunol. 2010;22(2):238–244.
58. Gabrilovich DI, Nagaraj S. Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol. 2009;9(3):162–174.
59. Hossain DM, Pal SK, Moreira D, et al. TLR9-targeted STAT3 silencing abrogates immunosuppressive activity of myeloid-derived suppressor cells from prostate cancer patients. Clin Cancer Res. 2015;21(16):3771–3782.
60. Sippel TR, White J, Nag K, et al. Neutrophil degranulation and immunosuppression in patients with GBM: restoration of cellular immune function by targeting arginase I. Clin Cancer Res. 2011;17(22):6992–7002.
61. Youn JI, Collazo M, Shalova IN, Biswas SK, Gabrilovich DI. Characterization of the nature of granulocytic myeloid-derived suppressor cells in tumor-bearing mice. J Leukoc Biol. 2012;91(1):167–181.
62. Fridlender ZG, Sun J, Mishalian I, et al. Transcriptomic analysis comparing tumor-associated neutrophils with granulocytic myeloid-derived suppressor cells and normal neutrophils. PLoS One. 2012;7(2):e31524.
63. Sagiv JY, Michaeli J, Assi S, et al. Phenotypic diversity and plasticity in circulating neutrophil subpopulations in cancer. Cell Rep. 2015;10(4):562–573.
64. Donskov F. Immunomonitoring and prognostic relevance of neutrophils in clinical trials. Semin Cancer Biol. 2013;23:200–207.
65. Jensen HK, Donskov F, Marcussen N, Nordsmark M, Lundbeck F, von der Maase H. Presence of intratumoral neutrophils is an independent prognostic factor in localized renal cell carcinoma. J Clin Oncol. 2009;27(28):4709–4717.
66. Rao HL, Chen JW, Li M, et al. Increased intratumoral neutrophil in colorectal carcinomas correlates closely with malignant phenotype and predicts patients' adverse prognosis. PLoS One. 2012;7(1):e30806.
67. Trellakis S, Bruderek K, Dumitru CA, et al. Polymorphonuclear granulocytes in human head and neck cancer: enhanced inflammatory activity, modulation by cancer cells and expansion in advanced disease. Int J Cancer. 2011;129(9):2183–2193.
68. Matsumoto Y, Mabuchi S, Kozasa K, et al. The significance of tumor-associated neutrophil density in uterine cervical cancer treated with definitive radiotherapy. Gynecol Oncol. 2017;145(3):469–475.
69. Fossati G, Ricevuti G, Edwards SW, Walker C, Dalton A, Rossi ML. Neutrophil infiltration into human gliomas. Acta Neuropathol. 1999;98(4):349–354.
70. Reid MD, Basturk O, Thirabanjasak D, et al. Tumor-infiltrating neutrophils in pancreatic neoplasia. Mod Pathol. 2011;24(12):1612–1619.
71. Gentles AJ, Newman AM, Liu CL, et al. The prognostic landscape of genes and infiltrating immune cells across human cancers. Nat Med. 2015;21(8):938–945.
72. Kargl J, Busch SE, Yang GH, et al. Neutrophils dominate the immune cell composition in non-small cell lung cancer. Nat Commun. 2017;8:14381.
73. Caruso RA, Bellocco R, Pagano M, Bertoli G, Rigoli L, Inferrera C. Prognostic value of intratumoral neutrophils in advanced gastric carcinoma in a high-risk area in northern Italy. Mod Pathol. 2002;15(8):831–837.
74. Galdiero MR, Bianchi P, Grizzi F, et al. Occurrence and significance of tumor-associated neutrophils in patients with colorectal cancer. Int J Cancer. 2016;139(2):446–456.
75. Droeser RA, Hirt C, Eppenberger-Castori S, et al. High myeloperoxidase positive cell infiltration in colorectal cancer is an independent favorable prognostic factor. PLoS One. 2013;8(5):e64814.
76. Shen J, Zhu Y, Wu W, et al. Prognostic role of neutrophil-to-lymphocyte ratio in locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy. Med Sci Monit. 2017;23:315–324.
77. Nakamura K, Yoshida N, Baba Y, et al. Elevated preoperative neutrophil-to-lymphocytes ratio predicts poor prognosis after esophagectomy in T1 esophageal cancer. Int J Clin Oncol. 2017.
78. Gokce MI, Tangal S, Hamidi N, Suer E, Ibis MA, Beduk Y. Role of neutrophil-to-lymphocyte ratio in prediction of Gleason score upgrading and disease upstaging in low-risk prostate cancer patients eligible for active surveillance. Can Urol Assoc J. 2016;10(11-12):E383–E387.
79. Kadokura M, Ishida Y, Tatsumi A, et al. Performance status and neutrophil-lymphocyte ratio are important prognostic factors in elderly patients with unresectable pancreatic cancer. J Gastrointest Oncol. 2016;7(6):982–988.
80. Ethier JL, Desautels D, Templeton A, Shah PS, Amir E. Prognostic role of neutrophil-to-lymphocyte ratio in breast cancer: a systematic review and meta-analysis. Breast Cancer Res. 2017;19(1):2.
81. Guthrie GJ, Charles KA, Roxburgh CS, Horgan PG, McMillan DC, Clarke SJ. The systemic inflammation-based neutrophil-lymphocyte ratio: experience in patients with cancer. Crit Rev Oncol Hematol. 2013;88(1):218–230.
82. Di Caro G, Marchesi F, Galdiero MR, Grizzi F. Immune mediators as potential diagnostic tools for colorectal cancer: from experimental rationale to early clinical evidence. Expert Rev Mol Diagn. 2014;14(3):387–399.
83. Ma Y, Adjemian S, Mattarollo SR, et al. Anticancer chemotherapy-induced intratumoral recruitment and differentiation of antigen-presenting cells. Immunity. 2013;38(4):729–741.
84. Galluzzi L, Senovilla L, Zitvogel L, Kroemer G. The secret ally: immunostimulation by anticancer drugs. Nat Rev Drug Discov. 2012;11(3):215–233.
85. Sharma P, Allison JP. The future of immune checkpoint therapy. Science. 2015;348(6230):56–61.
86. Bowers NL, Helton ES, Huijbregts RP, Goepfert PA, Heath SL, Hel Z. Immune suppression by neutrophils in HIV-1 infection: role of PD-L1/PD-1 pathway. PLoS Pathog. 2014;10(3):e1003993.
87. Wang JF, Li JB, Zhao YJ, et al. Up-regulation of programmed cell death 1 ligand 1 on neutrophils may be involved in sepsis-induced immunosuppression: an animal study and a prospective case-control study. Anesthesiology. 2015;122(4):852–863.
88. Buddhisa S, Rinchai D, Ato M, Bancroft GJ, Lertmemongkolchai G. Programmed death ligand 1 on Burkholderia pseudomallei-infected human polymorphonuclear neutrophils impairs T cell functions. J Immunol. 2015;194(9):4413–4421.
89. McNab FW, Berry MP, Graham CM, et al. Programmed death ligand 1 is over-expressed by neutrophils in the blood of patients with active tuberculosis. Eur J Immunol. 2011;41(7):1941–1947.
90. Luo Q, Huang Z, Ye J, et al. PD-L1-expressing neutrophils as a novel indicator to assess disease activity and severity of systemic lupus erythematosus. Arthritis Res Ther 2016;18:47.
91. Wang TT, Zhao YL, Peng LS, et al. Tumour-activated neutrophils in gastric cancer foster immune suppression and disease progression through GM-CSF-PD-L1 pathway. Gut. 2017;66:1900–1911.
92. Bekes EM, Schweighofer B, Kupriyanova TA, et al. Tumor-recruited neutrophils and neutrophil TIMP-free MMP-9 regulate coordinately the levels of tumor angiogenesis and efficiency of malignant cell intravasation. Am J Pathol. 2011;179(3):1455–1470.
93. Ginestier C, Liu S, Diebel ME, et al. CXCR1 blockade selectively targets human breast cancer stem cells in vitro and in xenografts. J Clin Invest. 2010;120(2):485–497.
94. Wang J, Hu W, Wang K, et al. Repertaxin, an inhibitor of the chemokine receptors CXCR1 and CXCR2, inhibits malignant behavior of human gastric cancer MKN45 cells in vitro and in vivo and enhances efficacy of 5-fluorouracil. Int J Oncol. 2016;48(4):1341–1352.
95. Nawa M, Osada S, Morimitsu K, et al. Growth effect of neutrophil elastase on breast cancer: favorable action of sivelestat and application to anti-HER2 therapy. Anticancer Res. 2012;32(1):13–19.
96. Starcher B, O'Neal P, Granstein RD, Beissert S. Inhibition of neutrophil elastase suppresses the development of skin tumors in hairless mice. J Invest Dermatol. 1996;107(2):159–163.
97. Inada M, Yamashita J, Nakano S, Ogawa M. Complete inhibition of spontaneous pulmonary metastasis of human lung carcinoma cell line EBC-1 by a neutrophil elastase inhibitor (ONO-5046.Na). Anticancer Res. 1998;18(2A):885–890.
98. Xue J, Zhao Z, Zhang L, et al. Neutrophil-mediated anticancer drug delivery for suppression of postoperative malignant glioma recurrence. Nat Nanotechnol. 2017;12:692–700.