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Annual Review of Cancer Biology

Volume 6, 2022

Caught in a Web: Emerging Roles of Neutrophil Extracellular Traps in Cancer

Abstract

Neutrophil extracellular traps (NETs) are meshes of DNA decorated with granular proteins that are extruded from neutrophils during immune responses to pathogens. However, excessive NET formation is negatively associated with many diseases, including cancer. NETs contain, for example, proteases, danger-associated molecular patterns (DAMPs), and DNA. These components can act directly on the cancer cells but also affect the surrounding microenvironment, including altering the extracellular matrix and the immune response to tumors. Here, we discuss the emerging roles of NETs in cancer progression, from their ability to promote primary tumor growth and immune escape to their prometastatic effects. The potential clinical implication of targeting NETs as novel therapeutic strategies in cancer is also discussed.

Keyword(s): extracellular DNA, immune microenvironment, metastases, neutrophil extracellular traps, proteases
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/content/journals/10.1146/annurev-cancerbio-080421-015537
2022-04-11
2024-04-27
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Literature Cited

  1. Abdol Razak N, Elaskalani O, Metharom P 2017. Pancreatic cancer-induced neutrophil extracellular traps: a potential contributor to cancer-associated thrombosis. Int. J. Mol. Sci. 18:487
     [Google Scholar]
  2. Acuff HB, Carter KJ, Fingleton B, Gorden DL, Matrisian LM 2006. . Matrix metalloproteinase-9 from bone marrow–derived cells contributes to survival but not growth of tumor cells in the lung microenvironment. Cancer Res 66:259–66
     [Google Scholar]
  3. Adrover JM, Aroca-Crevillen A, Crainiciuc G, Ostos F, Rojas-Vega Y et al. 2020. Programmed ‘disarming’ of the neutrophil proteome reduces the magnitude of inflammation. Nat. Immunol. 21:135–44
     [Google Scholar]
  4. Adrover JM, Carrau L, Daβler-Plenker J, Bram Y, Chandar V et al. 2022. Disulfiram inhibits neutrophil extracellular trap formation protecting rodents from acute lung injury and SARS-CoV-2 infection. JCI Insight 8:e157342
     [Google Scholar]
  5. Albrengues J, Shields MA, Ng D, Park CG, Ambrico A et al. 2018. Neutrophil extracellular traps produced during inflammation awaken dormant cancer cells in mice. Science 361:eaao4227
     [Google Scholar]
  6. Amulic B, Knackstedt SL, Abu Abed U, Deigendesch N, Harbort CJ et al. 2017. Cell-cycle proteins control production of neutrophil extracellular traps. Dev. Cell 43:449–62.e5
     [Google Scholar]
  7. An Z, Li J, Yu J, Wang X, Gao H et al. 2019. Neutrophil extracellular traps induced by IL-8 aggravate atherosclerosis via activation NF-κB signaling in macrophages. Cell Cycle 18:2928–38
     [Google Scholar]
  8. Arelaki S, Arampatzioglou A, Kambas K, Papagoras C, Miltiades P et al. 2016. Gradient infiltration of neutrophil extracellular traps in colon cancer and evidence for their involvement in tumour growth. PLOS ONE 11:e0154484
     [Google Scholar]
  9. Barnes BJ, Adrover JM, Baxter-Stoltzfus A, Borczuk A, Cools-Lartigue J et al. 2020. Targeting potential drivers of COVID-19: neutrophil extracellular traps. J. Exp. Med. 217:e20200652
     [Google Scholar]
  10. Berger-Achituv S, Brinkmann V, Abed UA, Kuhn LI, Ben-Ezra J et al. 2013. A proposed role for neutrophil extracellular traps in cancer immunoediting. Front Immunol 4:48
     [Google Scholar]
  11. Bergers G, Brekken R, McMahon G, Vu TH, Itoh T et al. 2000. Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis. Nat. Cell Biol. 2:737–44
     [Google Scholar]
  12. Borissoff JI, Joosen IA, Versteylen MO, Brill A, Fuchs TA et al. 2013. Elevated levels of circulating DNA and chromatin are independently associated with severe coronary atherosclerosis and a prothrombotic state. Arterioscler. Thromb. Vasc. Biol. 33:2032–40
     [Google Scholar]
  13. Brill A, Fuchs TA, Savchenko AS, Thomas GM, Martinod K et al. 2012. Neutrophil extracellular traps promote deep vein thrombosis in mice. J. Thromb. Haemost. 10:136–44
     [Google Scholar]
  14. Brinkmann V, Reichard U, Goosmann C, Fauler B, Uhlemann Y et al. 2004. Neutrophil extracellular traps kill bacteria. Science 303:1532–35
     [Google Scholar]
  15. Brinkmann V, Zychlinsky A. 2012. Neutrophil extracellular traps: Is immunity the second function of chromatin?. J. Cell Biol. 198:773–83
     [Google Scholar]
  16. Carmona-Rivera C, Zhao W, Yalavarthi S, Kaplan MJ 2015. Neutrophil extracellular traps induce endothelial dysfunction in systemic lupus erythematosus through the activation of matrix metalloproteinase-2. Ann. Rheum. Dis. 74:1417–24
     [Google Scholar]
  17. Casbon AJ, Reynaud D, Park C, Khuc E, Gan DD et al. 2015. Invasive breast cancer reprograms early myeloid differentiation in the bone marrow to generate immunosuppressive neutrophils. PNAS 112:E566–75
     [Google Scholar]
  18. Cedervall J, Zhang Y, Huang H, Zhang L, Femel J et al. 2015. Neutrophil extracellular traps accumulate in peripheral blood vessels and compromise organ function in tumor-bearing animals. Cancer Res 75:2653–62
     [Google Scholar]
  19. Chaffer CL, Weinberg RA. 2011. A perspective on cancer cell metastasis. Science 331:1559–64
     [Google Scholar]
  20. Chamilos G, Gregorio J, Meller S, Lande R, Kontoyiannis DP et al. 2012. Cytosolic sensing of extracellular self-DNA transported into monocytes by the antimicrobial peptide LL37. Blood 120:3699–707
     [Google Scholar]
  21. Chen KW, Monteleone M, Boucher D, Sollberger G, Ramnath D et al. 2018. Noncanonical inflammasome signaling elicits gasdermin D–dependent neutrophil extracellular traps. Sci. Immunol. 3:eaar6676
     [Google Scholar]
  22. Clancy DM, Sullivan GP, Moran HBT, Henry CM, Reeves EP et al. 2018. Extracellular neutrophil proteases are efficient regulators of IL-1, IL-33, and IL-36 cytokine activity but poor effectors of microbial killing. Cell Rep 22:2937–50
     [Google Scholar]
  23. Coffelt SB, Kersten K, Doornebal CW, Weiden J, Vrijland K et al. 2015. IL-17-producing γδ T cells and neutrophils conspire to promote breast cancer metastasis. Nature 522:345–48
     [Google Scholar]
  24. Cools-Lartigue J, Spicer J, McDonald B, Gowing S, Chow S et al. 2013. Neutrophil extracellular traps sequester circulating tumor cells and promote metastasis. J. Clin. Investig. 123:3446–58
     [Google Scholar]
  25. Cools-Lartigue J, Spicer J, Najmeh S, Ferri L 2014. Neutrophil extracellular traps in cancer progression. Cell Mol. Life Sci. 71:4179–94
     [Google Scholar]
  26. Coussens LM, Tinkle CL, Hanahan D, Werb Z 2000. MMP-9 supplied by bone marrow-derived cells contributes to skin carcinogenesis. Cell 103:481–90
     [Google Scholar]
  27. Cristinziano L, Modestino L, Antonelli A, Marone G, Simon HU et al. 2022. Neutrophil extracellular traps in cancer. Semin. Cancer Biol. 79:91–104
     [Google Scholar]
  28. Cui C, Chakraborty K, Tang XA, Zhou GL, Schoenfelt KQ et al. 2021. Neutrophil elastase selectively kills cancer cells and attenuates tumorigenesis. Cell 184:3163–77
     [Google Scholar]
  29. Davis JC Jr., Manzi S, Yarboro C, Rairie J, McInnes I et al. 1999. Recombinant human Dnase I (rhDNase) in patients with lupus nephritis. Lupus 8:68–76
     [Google Scholar]
  30. de Bont CM, Boelens WC, Pruijn GJM. 2019. NETosis, complement, and coagulation: a triangular relationship. Cell Mol. Immunol. 16:19–27
     [Google Scholar]
  31. Demers M, Krause DS, Schatzberg D, Martinod K, Voorhees JR et al. 2012. Cancers predispose neutrophils to release extracellular DNA traps that contribute to cancer-associated thrombosis. PNAS 109:13076–81
     [Google Scholar]
  32. Demers M, Wong SL, Martinod K, Gallant M, Cabral JE et al. 2016. Priming of neutrophils toward NETosis promotes tumor growth. OncoImmunology 5:e1134073
     [Google Scholar]
  33. Desilles JP, Gregoire C, Le Cossec C, Lambert J, Mophawe O et al. 2020. Efficacy and safety of aerosolized intra-tracheal dornase alfa administration in patients with SARS-CoV-2-induced acute respiratory distress syndrome (ARDS): a structured summary of a study protocol for a randomised controlled trial. Trials 21:548
     [Google Scholar]
  34. El Rayes T, Catena R, Lee S, Stawowczyk M, Joshi N et al. 2015. Lung inflammation promotes metastasis through neutrophil protease-mediated degradation of Tsp-1. PNAS 112:16000–5
     [Google Scholar]
  35. Etulain J, Martinod K, Wong SL, Cifuni SM, Schattner M, Wagner DD. 2015. P-selectin promotes neutrophil extracellular trap formation in mice. Blood 126:242–46
     [Google Scholar]
  36. Farrera C, Fadeel B. 2013. Macrophage clearance of neutrophil extracellular traps is a silent process. J. Immunol. 191:2647–56
     [Google Scholar]
  37. Fernandes-Alnemri T, Yu JW, Datta P, Wu J, Alnemri ES. 2009. AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA. Nature 458:509–13
     [Google Scholar]
  38. Fernandes CJ, Morinaga LTK, Alves JL, Castro MA, Calderaro D et al. 2019. Cancer-associated thrombosis: the when, how and why. Eur. Respir. Rev. 28:180119
     [Google Scholar]
  39. Fuchs TA, Brill A, Duerschmied D, Schatzberg D, Monestier M et al. 2010. Extracellular DNA traps promote thrombosis. PNAS 107:15880–85
     [Google Scholar]
  40. Gabrilovich DI, Nagaraj S. 2009. Myeloid-derived suppressor cells as regulators of the immune system. Nat. Rev. Immunol. 9:162–74
     [Google Scholar]
  41. Gaida MM, Steffen TG, Gunther F, Tschaharganeh DF, Felix K et al. 2012. Polymorphonuclear neutrophils promote dyshesion of tumor cells and elastase-mediated degradation of E-cadherin in pancreatic tumors. Eur. J. Immunol. 42:3369–80
     [Google Scholar]
  42. Gomes T, Varady CBS, Lourenco AL, Mizurini DM, Rondon AMR et al. 2019. IL-1β blockade attenuates thrombosis in a neutrophil extracellular trap-dependent breast cancer model. Front. Immunol. 10:2088
     [Google Scholar]
  43. Gong L, Cumpian AM, Caetano MS, Ochoa CE, De la Garza MM et al. 2013. Promoting effect of neutrophils on lung tumorigenesis is mediated by CXCR2 and neutrophil elastase. Mol. Cancer 12:154
     [Google Scholar]
  44. Gonzalez-Aparicio M, Alfaro C. 2019. Influence of interleukin-8 and neutrophil extracellular trap (net) formation in the tumor microenvironment: Is there a pathogenic role?. J. Immunol. Res. 2019:6252138
     [Google Scholar]
  45. Grayson PC, Kaplan MJ. 2016. At the bench: Neutrophil extracellular traps (NETs) highlight novel aspects of innate immune system involvement in autoimmune diseases. J. Leukoc. Biol. 99:253–64
     [Google Scholar]
  46. Gregory AD, Hale P, Perlmutter DH, Houghton AM. 2012. Clathrin pit-mediated endocytosis of neutrophil elastase and cathepsin G by cancer cells. J. Biol. Chem. 287:35341–50
     [Google Scholar]
  47. Grosse-Steffen T, Giese T, Giese N, Longerich T, Schirmacher P et al. 2012. Epithelial-to-mesenchymal transition in pancreatic ductal adenocarcinoma and pancreatic tumor cell lines: the role of neutrophils and neutrophil-derived elastase. Clin. Dev. Immunol. 2012:720768
     [Google Scholar]
  48. Guiducci E, Lemberg C, Kung N, Schraner E, Theocharides APA, LeibundGut-Landmann S. 2018. Candida albicans-induced NETosis is independent of peptidylarginine deiminase 4. Front. Immunol. 9:1573
     [Google Scholar]
  49. Haider P, Kral-Pointner JB, Mayer J, Richter M, Kaun C et al. 2020. Neutrophil extracellular trap degradation by differently polarized macrophage subsets. Arterioscler. Thromb. Vasc. Biol. 40:2265–78
     [Google Scholar]
  50. Hakkim A, Fuchs TA, Martinez NE, Hess S, Prinz H et al. 2011. Activation of the Raf-MEK-ERK pathway is required for neutrophil extracellular trap formation. Nat. Chem. Biol. 7:75–77
     [Google Scholar]
  51. Halverson TWR, Wilton M, Poon KKH, Petri B, Lewenza S 2015. DNA is an antimicrobial component of neutrophil extracellular traps. PLOS Pathog 11:e1004593
     [Google Scholar]
  52. Hanahan D, Weinberg RA. 2011. Hallmarks of cancer: the next generation. Cell 144:646–74
     [Google Scholar]
  53. Ho AS, Chen CH, Cheng CC, Wang CC, Lin HC et al. 2014. Neutrophil elastase as a diagnostic marker and therapeutic target in colorectal cancers. Oncotarget 5:473–80
     [Google Scholar]
  54. Hornung V, Ablasser A, Charrel-Dennis M, Bauernfeind F, Horvath G et al. 2009. AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC. Nature 458:514–18
     [Google Scholar]
  55. Houghton AM, Rzymkiewicz DM, Ji H, Gregory AD, Egea EE et al. 2010. Neutrophil elastase-mediated degradation of IRS-1 accelerates lung tumor growth. Nat. Med. 16:219–23
     [Google Scholar]
  56. Hu JJ, Liu X, Xia S, Zhang Z, Zhang Y et al. 2020. FDA-approved disulfiram inhibits pyroptosis by blocking gasdermin D pore formation. Nat. Immunol. 21:736–45
     [Google Scholar]
  57. Hu QY, Shi H, Zeng T, Liu HL, Su YT et al. 2019. Increased neutrophil extracellular traps activate NLRP3 and inflammatory macrophages in adult-onset Still's disease. Arthritis Res. Ther. 21:9
     [Google Scholar]
  58. Jaillon S, Peri G, Delneste Y, Fremaux I, Doni A et al. 2007. The humoral pattern recognition receptor PTX3 is stored in neutrophil granules and localizes in extracellular traps. J. Exp. Med. 204:793–804
     [Google Scholar]
  59. Jin C, Lagoudas GK, Zhao C, Bullman S, Bhutkar A et al. 2019. Commensal microbiota promote lung cancer development via γδ T cells. Cell 176:998–1013.e16
     [Google Scholar]
  60. Jin L, Batra S, Jeyaseelan S 2017. Diminished neutrophil extracellular trap (NET) formation is a novel innate immune deficiency induced by acute ethanol exposure in polymicrobial sepsis, which can be rescued by CXCL1. PLOS Pathog 13:e1006637
     [Google Scholar]
  61. Jung HS, Gu J, Kim JE, Nam Y, Song JW, Kim HK. 2019. Cancer cell–induced neutrophil extracellular traps promote both hypercoagulability and cancer progression. PLOS ONE 14:e0216055
     [Google Scholar]
  62. Kahlenberg JM, Carmona-Rivera C, Smith CK, Kaplan MJ. 2013. Neutrophil extracellular trap–associated protein activation of the NLRP3 inflammasome is enhanced in lupus macrophages. J. Immunol. 190:1217–26
     [Google Scholar]
  63. Kantari C, Pederzoli-Ribeil M, Witko-Sarsat V. 2008. The role of neutrophils and monocytes in innate immunity. Contrib. Microbiol. 15:118–46
     [Google Scholar]
  64. Kawahara Y, Ninomiya I, Fujimura T, Funaki H, Nakagawara H et al. 2010. Prospective randomized controlled study on the effects of perioperative administration of a neutrophil elastase inhibitor to patients undergoing video-assisted thoracoscopic surgery for thoracic esophageal cancer. Dis. Esophagus 23:329–39
     [Google Scholar]
  65. Kawai T, Akira S. 2010. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat. Immunol. 11:373–84
     [Google Scholar]
  66. Kessenbrock K, Krumbholz M, Schonermarck U, Back W, Gross WL et al. 2009. Netting neutrophils in autoimmune small-vessel vasculitis. Nat. Med. 15:623–25
     [Google Scholar]
  67. Kessenbrock K, Plaks V, Werb Z 2010. Matrix metalloproteinases: regulators of the tumor microenvironment. Cell 141:52–67
     [Google Scholar]
  68. Knight JS, Luo W, O'Dell AA, Yalavarthi S, Zhao WP et al. 2014. Peptidylarginine deiminase inhibition reduces vascular damage and modulates innate immune responses in murine models of atherosclerosis. Circ. Res. 114:947–56
     [Google Scholar]
  69. Kolaczkowska E, Kubes P. 2013. Neutrophil recruitment and function in health and inflammation. Nat. Rev. Immunol. 13:159–75
     [Google Scholar]
  70. Landoni VI, Chiarella P, Martire-Greco D, Schierloh P, van-Rooijen N et al. 2012. Tolerance to lipopolysaccharide promotes an enhanced neutrophil extracellular traps formation leading to a more efficient bacterial clearance in mice. Clin. Exp. Immunol. 168:153–63
     [Google Scholar]
  71. Lauth X, von Kockritz-Blickwede M, McNamara CW, Myskowski S, Zinkernagel AS et al. 2009. M1 protein allows group A streptococcal survival in phagocyte extracellular traps through cathelicidin inhibition. J. Innate Immun. 1:202–14
     [Google Scholar]
  72. Lazzaretto B, Fadeel B. 2019. Intra- and extracellular degradation of neutrophil extracellular traps by macrophages and dendritic cells. J. Immunol. 203:2276–90
     [Google Scholar]
  73. Lee W, Ko SY, Mohamed MS, Kenny HA, Lengyel E, Naora H 2019. Neutrophils facilitate ovarian cancer premetastatic niche formation in the omentum. J. Exp. Med. 216:176–94
     [Google Scholar]
  74. Lefrancais E, Mallavia B, Zhuo H, Calfee CS, Looney MR. 2018. Maladaptive role of neutrophil extracellular traps in pathogen-induced lung injury. JCI Insight 3:e98178
     [Google Scholar]
  75. Lefrancais E, Roga S, Gautier V, Gonzalez-de-Peredo A, Monsarrat B et al. 2012. IL-33 is processed into mature bioactive forms by neutrophil elastase and cathepsin G. PNAS 109:1673–78
     [Google Scholar]
  76. Leon SA, Shapiro B, Sklaroff DM, Yaros MJ. 1977. Free DNA in the serum of cancer patients and the effect of therapy. Cancer Res 37:646–50
     [Google Scholar]
  77. Li PX, Li M, Lindberg MR, Kennett MJ, Xiong N, Wang YM. 2010. PAD4 is essential for antibacterial innate immunity mediated by neutrophil extracellular traps. J. Exp. Med. 207:1853–62
     [Google Scholar]
  78. Li Y, Yang Y, Gan T, Zhou J, Hu F et al. 2019. Extracellular RNAs from lung cancer cells activate epithelial cells and induce neutrophil extracellular traps. Int. J. Oncol. 55:69–80
     [Google Scholar]
  79. Linhares-Lacerda L, Temerozo JR, Ribeiro-Alves M, Azevedo EP, Mojoli A et al. 2020. Neutrophil extracellular trap-enriched supernatants carry microRNAs able to modulate TNF-α production by macrophages. Sci. Rep. 10:2715
     [Google Scholar]
  80. Liu K, Sun E, Lei M, Li L, Gao J et al. 2019. BCG-induced formation of neutrophil extracellular traps play an important role in bladder cancer treatment. Clin. Immunol. 201:4–14
     [Google Scholar]
  81. Liu YD, Carmona-Rivera C, Moore E, Seto NL, Knight JS et al. 2018. Myeloid-specific deletion of peptidyl-arginine deiminase 4 mitigates atherosclerosis. Front. Immunol. 9:1680
     [Google Scholar]
  82. Ma YH, Ma TT, Wang C, Wang H, Chang DY et al. 2016. High-mobility group box 1 potentiates antineutrophil cytoplasmic antibody-inducing neutrophil extracellular traps formation. Arthritis Res. Ther. 18:2
     [Google Scholar]
  83. Maksimov P, Hermosilla C, Kleinertz S, Hirzmann J, Taubert A. 2016. Besnoitia besnoiti infections activate primary bovine endothelial cells and promote PMN adhesion and NET formation under physiological flow condition. Parasitol. Res. 115:1991–2001
     [Google Scholar]
  84. Maksimowicz T, Chyczewska E, Chyczewski L, Niklinski J, Ostrowska H et al. 1997. Activity and tissue localization of cathepsin G in non small cell lung cancer. Rocz. Akad. Med. Bialymst. 42:1199–216
     [Google Scholar]
  85. Mantovani A, Cassatella MA, Costantini C, Jaillon S 2011. Neutrophils in the activation and regulation of innate and adaptive immunity. Nat. Rev. Immunol. 11:519–31
     [Google Scholar]
  86. Martins-Cardoso K, Almeida VH, Bagri KM, Rossi MID, Mermelstein CS et al. 2020. Neutrophil extracellular traps (NETs) promote pro-metastatic phenotype in human breast cancer cells through epithelial-mesenchymal transition. Cancers 12:1542
     [Google Scholar]
  87. Massberg S, Grahl L, von Bruehl ML, Manukyan D, Pfeiler S et al. 2010. Reciprocal coupling of coagulation and innate immunity via neutrophil serine proteases. Nat. Med. 16:887–96
     [Google Scholar]
  88. Maugeri N, Campana L, Gavina M, Covino C, De Metrio M et al. 2014. Activated platelets present high mobility group box 1 to neutrophils, inducing autophagy and promoting the extrusion of neutrophil extracellular traps. J. Thromb. Haemost. 12:2074–88
     [Google Scholar]
  89. Mauracher LM, Posch F, Martinod K, Grilz E, Daullary T et al. 2018. Citrullinated histone H3, a biomarker of neutrophil extracellular trap formation, predicts the risk of venous thromboembolism in cancer patients. J. Thromb. Haemost. 16:508–18
     [Google Scholar]
  90. Mayadas TN, Cullere X, Lowell CA 2014. The multifaceted functions of neutrophils. Annu. Rev. Pathol. Mech. Dis. 9:181–218
     [Google Scholar]
  91. McDonald B, Spicer J, Giannais B, Fallavollita L, Brodt P, Ferri LE. 2009. Systemic inflammation increases cancer cell adhesion to hepatic sinusoids by neutrophil mediated mechanisms. Int. J. Cancer 125:1298–305
     [Google Scholar]
  92. McLoed AG, Sherrill TP, Cheng DS, Han W, Saxon JA et al. 2016. Neutrophil-derived IL-1β impairs the efficacy of NF-κB inhibitors against lung cancer. Cell Rep 16:120–32
     [Google Scholar]
  93. Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS et al. 2020. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet 395:1033–34
     [Google Scholar]
  94. Middleton EA, He XY, Denorme F, Campbell RA, Ng D et al. 2020. Neutrophil extracellular traps contribute to immunothrombosis in COVID-19 acute respiratory distress syndrome. Blood 136:1169–79
     [Google Scholar]
  95. Miller-Ocuin JL, Liang X, Boone BA, Doerfler WR, Singhi AD et al. 2019. DNA released from neutrophil extracellular traps (NETs) activates pancreatic stellate cells and enhances pancreatic tumor growth. OncoImmunology 8:e1605822
     [Google Scholar]
  96. Mishalian I, Bayuh R, Eruslanov E, Michaeli J, Levy L et al. 2014. Neutrophils recruit regulatory T-cells into tumors via secretion of CCL17—a new mechanism of impaired antitumor immunity. Int. J. Cancer 135:1178–86
     [Google Scholar]
  97. Mitroulis I, Kambas K, Chrysanthopoulou A, Skendros P, Apostolidou E et al. 2011. Neutrophil extracellular trap formation is associated with IL-1β and autophagy-related signaling in gout. PLOS ONE 6:e29318
     [Google Scholar]
  98. Morimoto-Kamata R, Yui S. 2017. Insulin-like growth factor-1 signaling is responsible for cathepsin G-induced aggregation of breast cancer MCF-7 cells. Cancer Sci 108:1574–83
     [Google Scholar]
  99. Munir H, Jones JO, Janowitz T, Hoffmann M, Euler M et al. 2021. Stromal-driven and Amyloid β-dependent induction of neutrophil extracellular traps modulates tumor growth. Nat. Commun. 12:683
     [Google Scholar]
  100. Munzer P, Negro R, Fukui S, di Meglio L, Aymonnier K et al. 2021. NLRP3 inflammasome assembly in neutrophils is supported by PAD4 and promotes NETosis under sterile conditions. Front. Immunol. 12:683803
     [Google Scholar]
  101. Mutua V, Gershwin LJ. 2021. A review of neutrophil extracellular traps (NETs) in disease: potential anti-NETs therapeutics. Clin. Rev. Allergy Immunol. 61:194–211
     [Google Scholar]
  102. Najmeh S, Cools-Lartigue J, Rayes RF, Gowing S, Vourtzoumis P et al. 2017. Neutrophil extracellular traps sequester circulating tumor cells via β1-integrin mediated interactions. Int. J. Cancer 140:2321–30
     [Google Scholar]
  103. Nawa M, Osada S, Morimitsu K, Nonaka K, Futamura M et al. 2012. Growth effect of neutrophil elastase on breast cancer: favorable action of sivelestat and application to anti-HER2 therapy. Anticancer Res 32:13–19
     [Google Scholar]
  104. Neeli I, Khan SN, Radic M. 2008. Histone deimination as a response to inflammatory stimuli in neutrophils. J. Immunol. 180:1895–902
     [Google Scholar]
  105. Nie M, Yang L, Bi X, Wang Y, Sun P et al. 2019. Neutrophil extracellular traps induced by IL8 promote diffuse large B-cell lymphoma progression via the TLR9 signaling. Clin. Cancer Res. 25:1867–79
     [Google Scholar]
  106. Nozawa H, Chiu C, Hanahan D. 2006. Infiltrating neutrophils mediate the initial angiogenic switch in a mouse model of multistage carcinogenesis. PNAS 103:12493–98
     [Google Scholar]
  107. Nywening TM, Belt BA, Cullinan DR, Panni RZ, Han BJ et al. 2018. Targeting both tumour-associated CXCR2+ neutrophils and CCR2+ macrophages disrupts myeloid recruitment and improves chemotherapeutic responses in pancreatic ductal adenocarcinoma. Gut 67:1112–23
     [Google Scholar]
  108. Papayannopoulos V. 2018. Neutrophil extracellular traps in immunity and disease. Nat. Rev. Immunol. 18:134–47
     [Google Scholar]
  109. Papayannopoulos V, Metzler KD, Hakkim A, Zychlinsky A. 2010. Neutrophil elastase and myeloperoxidase regulate the formation of neutrophil extracellular traps. J. Cell Biol. 191:677–91
     [Google Scholar]
  110. Park J, Wysocki RW, Amoozgar Z, Maiorino L, Fein MR et al. 2016. Cancer cells induce metastasis-supporting neutrophil extracellular DNA traps. Sci. Transl. Med. 8:361ra138
     [Google Scholar]
  111. Park JH, Rasch MG, Qiu J, Lund IK, Egeblad M. 2015. Presence of insulin-like growth factor binding proteins correlates with tumor-promoting effects of matrix metalloproteinase 9 in breast cancer. Neoplasia 17:421–33
     [Google Scholar]
  112. Parker H, Dragunow M, Hampton MB, Kettle AJ, Winterbourn CC. 2012. Requirements for NADPH oxidase and myeloperoxidase in neutrophil extracellular trap formation differ depending on the stimulus. J. Leukoc. Biol. 92:841–49
     [Google Scholar]
  113. Patutina O, Mironova N, Ryabchikova E, Popova N, Nikolin V et al. 2011. Inhibition of metastasis development by daily administration of ultralow doses of RNase A and DNase I. Biochimie 93:689–96
     [Google Scholar]
  114. Peng Z, Liu C, Victor AR, Cao DY, Veiras LC et al. 2021. Tumors exploit CXCR4hiCD62Llo aged neutrophils to facilitate metastatic spread. OncoImmunology 10:1870811
     [Google Scholar]
  115. Pham CTN. 2006. Neutrophil serine proteases: specific regulators of inflammation. Nat. Rev. Immunol. 6:541–50
     [Google Scholar]
  116. Pillai PS, Molony RD, Martinod K, Dong H, Pang IK et al. 2016. Mx1 reveals innate pathways to antiviral resistance and lethal influenza disease. Science 352:463–66
     [Google Scholar]
  117. Quan JM, Tiddens HA, Sy JP, McKenzie SG, Montgomery MD et al. 2001. A two-year randomized, placebo-controlled trial of dornase alfa in young patients with cystic fibrosis with mild lung function abnormalities. J. Pediatr. 139:813–20
     [Google Scholar]
  118. Raftery MJ, Lalwani P, Krautkrmer E, Peters T, Scharffetter-Kochanek K et al. 2014. β2 integrin mediates hantavirus-induced release of neutrophil extracellular traps. J. Exp. Med. 211:1485–97
     [Google Scholar]
  119. Rayes RF, Mouhanna JG, Nicolau I, Bourdeau F, Giannias B et al. 2019. Primary tumors induce neutrophil extracellular traps with targetable metastasis promoting effects. JCI Insight 5:e128008
     [Google Scholar]
  120. Ren J, He J, Zhang H, Xia Y, Hu Z et al. 2021. Platelet TLR4-ERK5 axis facilitates NET-mediated capturing of circulating tumor cells and distant metastasis after surgical stress. Cancer Res 81:2373–85
     [Google Scholar]
  121. Richardson JJR, Hendrickse C, Gao-Smith F, Thickett DR. 2017. Characterization of systemic neutrophil function in patients undergoing colorectal cancer resection. J. Surg. Res. 220:410–18.e1
     [Google Scholar]
  122. Segal AW. 2005. How neutrophils kill microbes. Annu. Rev. Immunol. 23:197–223
     [Google Scholar]
  123. Semeraro F, Ammollo CT, Morrissey JH, Dale GL, Friese P et al. 2011. Extracellular histones promote thrombin generation through platelet-dependent mechanisms: involvement of platelet TLR2 and TLR4. Blood 118:1952–61
     [Google Scholar]
  124. Seo JD, Gu JY, Jung HS, Kim YJ, Kim HK 2019. Contact system activation and neutrophil extracellular trap markers: risk factors for portal vein thrombosis in patients with hepatocellular carcinoma. Clin. Appl. Thromb. Hemost. 25:1076029618825310
     [Google Scholar]
  125. Shi J, Zhao Y, Wang K, Shi X, Wang Y et al. 2015. Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death. Nature 526:660–65
     [Google Scholar]
  126. Smith HA, Kang Y. 2013. The metastasis-promoting roles of tumor-associated immune cells. J. Mol. Med. 91:411–29
     [Google Scholar]
  127. Snoderly HT, Boone BA, Bennewitz MF. 2019. Neutrophil extracellular traps in breast cancer and beyond: current perspectives on NET stimuli, thrombosis and metastasis, and clinical utility for diagnosis and treatment. Breast Cancer Res 21:145
     [Google Scholar]
  128. Soehnlein O, Lindbom L. 2010. Phagocyte partnership during the onset and resolution of inflammation. Nat. Rev. Immunol. 10:427–39
     [Google Scholar]
  129. Sollberger G, Choidas A, Burn GL, Habenberger P, Di Lucrezia R et al. 2018. Gasdermin D plays a vital role in the generation of neutrophil extracellular traps. Sci. Immunol. 3:eaar6689
     [Google Scholar]
  130. Spicer JD, McDonald B, Cools-Lartigue JJ, Chow SC, Giannias B et al. 2012. Neutrophils promote liver metastasis via Mac-1–mediated interactions with circulating tumor cells. Cancer Res 72:3919–27
     [Google Scholar]
  131. Spiegel A, Brooks MW, Houshyar S, Reinhardt F, Ardolino M et al. 2016. Neutrophils suppress intraluminal NK cell–mediated tumor cell clearance and enhance extravasation of disseminated carcinoma cells. Cancer Discov 6:630–49
     [Google Scholar]
  132. Sugihara S, Yamamoto T, Tanaka H, Kambara T, Hiraoka T, Miyauchi Y. 1993. Deoxyribonuclease treatment prevents blood-borne liver metastasis of cutaneously transplanted tumour cells in mice. Br. J. Cancer 67:66–70
     [Google Scholar]
  133. Sun L, Kees T, Almeida AS, Liu B, He X-Y et al. 2021. Activating a collaborative innate-adaptive immune response to control breast and ovarian cancer metastasis. Cancer Cell 39:1361–74.e9
     [Google Scholar]
  134. Sun L, Wu J, Du F, Chen X, Chen ZJ 2013. Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway. Science 339:786–91
     [Google Scholar]
  135. Szczerba BM, Castro-Giner F, Vetter M, Krol I, Gkountela S et al. 2019. Neutrophils escort circulating tumour cells to enable cell cycle progression. Nature 566:553–57
     [Google Scholar]
  136. Tadie JM, Bae HB, Jiang SN, Park DW, Bell CP et al. 2013. HMGB1 promotes neutrophil extracellular trap formation through interactions with Toll-like receptor 4. Am. J. Physiol. Lung Cell. Mol. Physiol. 304:L342–49
     [Google Scholar]
  137. Teijeira A, Garasa S, Gato M, Alfaro C, Migueliz I et al. 2020. CXCR1 and CXCR2 chemokine receptor agonists produced by tumors induce neutrophil extracellular traps that interfere with immune cytotoxicity. Immunity 52:856–71
     [Google Scholar]
  138. Thalin C, Demers M, Blomgren B, Wong SL, von Arbin M et al. 2016. NETosis promotes cancer-associated arterial microthrombosis presenting as ischemic stroke with troponin elevation. Thromb. Res. 139:56–64
     [Google Scholar]
  139. Thalin C, Lundstrom S, Seignez C, Daleskog M, Lundstrom A et al. 2018. Citrullinated histone H3 as a novel prognostic blood marker in patients with advanced cancer. PLOS ONE 13:e0191231
     [Google Scholar]
  140. Thomas GM, Carbo C, Curtis BR, Martinod K, Mazo IB et al. 2012. Extracellular DNA traps are associated with the pathogenesis of TRALI in humans and mice. Blood 119:6335–43
     [Google Scholar]
  141. Tillack K, Breiden P, Martin R, Sospedra M. 2012. T lymphocyte priming by neutrophil extracellular traps links innate and adaptive immune responses. J. Immunol. 188:3150–59
     [Google Scholar]
  142. Tohme S, Yazdani HO, Al-Khafaji AB, Chidi AP, Loughran P et al. 2016. Neutrophil extracellular traps promote the development and progression of liver metastases after surgical stress. Cancer Res 76:1367–80
     [Google Scholar]
  143. Urban CF, Ermert D, Schmid M, Abu-Abed U, Goosmann C et al. 2009. Neutrophil extracellular traps contain calprotectin, a cytosolic protein complex involved in host defense against Candida albicans. PLOS Pathog 5:e1000639
     [Google Scholar]
  144. van der Windt DJ, Sud V, Zhang H, Varley PR, Goswami J et al. 2018. Neutrophil extracellular traps promote inflammation and development of hepatocellular carcinoma in nonalcoholic steatohepatitis. Hepatology 68:1347–60
     [Google Scholar]
  145. Veras FP, Pontelli MC, Silva CM, Toller-Kawahisa JE, de Lima M et al. 2020. SARS-CoV-2-triggered neutrophil extracellular traps mediate COVID-19 pathology. J. Exp. Med. 217:e20201129
     [Google Scholar]
  146. Wada Y, Yoshida K, Hihara J, Konishi K, Tanabe K et al. 2006. Sivelestat, a specific neutrophil elastase inhibitor, suppresses the growth of gastric carcinoma cells by preventing the release of transforming growth factor-α. Cancer Sci 97:1037–43
     [Google Scholar]
  147. Wada Y, Yoshida K, Tsutani Y, Shigematsu H, Oeda M et al. 2007. Neutrophil elastase induces cell proliferation and migration by the release of TGF-α, PDGF and VEGF in esophageal cell lines. Oncol. Rep. 17:161–67
     [Google Scholar]
  148. Wang Z, Yang C, Li L, Jin X, Zhang Z et al. 2020. Tumor-derived HMGB1 induces CD62Ldim neutrophil polarization and promotes lung metastasis in triple-negative breast cancer. Oncogenesis 9:82
     [Google Scholar]
  149. Warnatsch A, Ioannou M, Wang Q, Papayannopoulos V 2015. Neutrophil extracellular traps license macrophages for cytokine production in atherosclerosis. Science 349:316–20
     [Google Scholar]
  150. Weber AG, Chau AS, Egeblad M, Barnes BJ, Janowitz T. 2020. Nebulized in-line endotracheal dornase alfa and albuterol administered to mechanically ventilated COVID-19 patients: a case series. Mol. Med. 26:91
     [Google Scholar]
  151. Weinrauch Y, Drujan D, Shapiro SD, Weiss J, Zychlinsky A. 2002. Neutrophil elastase targets virulence factors of enterobacteria. Nature 417:91–94
     [Google Scholar]
  152. Wen F, Shen A, Choi A, Gerner EW, Shi J. 2013. Extracellular DNA in pancreatic cancer promotes cell invasion and metastasis. Cancer Res 73:4256–66
     [Google Scholar]
  153. Wilson TJ, Nannuru KC, Futakuchi M, Sadanandam A, Singh RK. 2008. Cathepsin G enhances mammary tumor-induced osteolysis by generating soluble receptor activator of nuclear factor-κB ligand. Cancer Res 68:5803–11
     [Google Scholar]
  154. Wilson TJ, Nannuru KC, Futakuchi M, Singh RK 2010. Cathepsin G-mediated enhanced TGF-β signaling promotes angiogenesis via upregulation of VEGF and MCP-1. Cancer Lett 288:162–69
     [Google Scholar]
  155. Wilson TJ, Nannuru KC, Singh RK. 2009. Cathepsin G–mediated activation of pro–matrix metalloproteinase 9 at the tumor-bone interface promotes transforming growth factor-β signaling and bone destruction. Mol. Cancer Res. 7:1224–33
     [Google Scholar]
  156. Xia Y, He J, Zhang H, Wang H, Tetz G et al. 2020. AAV-mediated gene transfer of DNase I in the liver of mice with colorectal cancer reduces liver metastasis and restores local innate and adaptive immune response. Mol. Oncol. 14:2920–35
     [Google Scholar]
  157. Xiao Y, Cong M, Li J, He D, Wu Q et al. 2020. Cathepsin C promotes breast cancer lung metastasis by modulating neutrophil infiltration and neutrophil extracellular trap formation. Cancer Cell 39:423–37
     [Google Scholar]
  158. Yang C, Montgomery M 2021. Dornase alfa for cystic fibrosis. Cochrane Database Syst. Rev. 3:CD001127
     [Google Scholar]
  159. Yang C, Sun W, Cui W, Li X, Yao J et al. 2015. Procoagulant role of neutrophil extracellular traps in patients with gastric cancer. Int. J. Clin. Exp. Pathol. 8:14075–86
     [Google Scholar]
  160. Yang L, Liu Q, Zhang X, Liu X, Zhou B et al. 2020. DNA of neutrophil extracellular traps promotes cancer metastasis via CCDC25. Nature 583:133–38
     [Google Scholar]
  161. Yazdani HO, Roy E, Comerci AJ, van der Windt DJ, Zhang H et al. 2019. Neutrophil extracellular traps drive mitochondrial homeostasis in tumors to augment growth. Cancer Res 79:5626–39
     [Google Scholar]
  162. Zhang Y, Chandra V, Riquelme Sanchez E, Dutta P, Quesada PR et al. 2020a. Interleukin-17–induced neutrophil extracellular traps mediate resistance to checkpoint blockade in pancreatic cancer. J. Exp. Med. 217:e20190354
     [Google Scholar]
  163. Zhang Y, Hu Y, Ma C, Sun H, Wei X et al. 2020b. Diagnostic, therapeutic predictive, and prognostic value of neutrophil extracellular traps in patients with gastric adenocarcinoma. Front. Oncol. 10:1036
     [Google Scholar]
  164. Zuo Y, Yalavarthi S, Shi H, Gockman K, Zuo M et al. 2020. Neutrophil extracellular traps in COVID-19. JCI Insight 5:e138999
     [Google Scholar]
  165. Zuo Y, Zuo M, Yalavarthi S, Gockman K, Madison JA et al. 2021. Neutrophil extracellular traps and thrombosis in COVID-19. J. Thromb. Thrombolysis 51:446–53
     [Google Scholar]
/content/journals/10.1146/annurev-cancerbio-080421-015537
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Caught in a Web: Emerging Roles of Neutrophil Extracellular Traps in Cancer
Annual Review of Cancer Biology 6, 223 (2022); https://doi.org/10.1146/annurev-cancerbio-080421-015537
/content/journals/10.1146/annurev-cancerbio-080421-015537
/content/journals/10.1146/annurev-cancerbio-080421-015537
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