Neutrophils in cancer: Insights from intravital imaging

Sapna Devi

*Correspondence to: Sapna Devi, Department of Microbiology and Immunology, The University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia. E-mail: sapna.devi@unimelb.edu.au

Myeloid Cells. 2026;1:202607. 10.70401/mc.2026.0007

Received: April 05, 2026Accepted: June 29, 2026Published: June 30, 2026

This manuscript is made available in its unedited form to allow early access to the reported findings. Further editing will be completed before final publication. As such, the content may include errors, and standard legal disclaimers are applicable.

Abstract

Multiple clinical and translational studies have shown that infiltration of tumour-associated neutrophils is associated with advanced disease stages, increased metastatic spread, therapeutic resistance, and poorer overall survival across various cancer types. Beyond their traditional role as first responders to tissue damage and pathogen infection, neutrophils within the tumour microenvironment (TME) display remarkable functional plasticity, adopting phenotypes that can promote angiogenesis, extracellular matrix remodelling, immune suppression, and tumour cell invasion. Importantly, it is now recognised that the prognostic impact of neutrophils is highly context-dependent, shaped by tumour type, stage, and the evolving inflammatory milieu. Intravital imaging studies have revealed dynamic neutrophil behaviours, including distinct migratory patterns between intra-tumoural and peri-tumoural regions, interactions with tumour and immune cells, and contributions to processes such as metastasis and immune suppression. However, there is a lack of understanding of how transcriptionally defined neutrophil subsets translate into specific functional and behavioural states in the TME in vivo. This mini-review spotlights intravital imaging approaches that illuminate neutrophil dynamics in tumours. We also discuss how extrinsic regulators, including cancer-associated fibroblasts and neural inputs direct neutrophil dynamics, further contributing to TME complexity.

Keywords

Neutrophils, intravital imaging, tumour microenvironment, cancer

References

1. Pittet MJ, Weissleder R. Intravital imaging. Cell. 2011;147(5):983-991.

[DOI]
2. Deniset JF, Kubes P. Intravital imaging of myeloid cells: Inflammatory migration and resident patrolling. Microbiol Spectr. 2016.

[DOI] [PubMed]
3. Pittet MJ, Garris CS, Arlauckas SP, Weissleder R. Recording the wild lives of immune cells. Sci Immunol. 2018;3(27):eaaq0491.

[DOI]
4. Condeelis J, Segall JE. Intravital imaging of cell movement in tumours. Nat Rev Cancer. 2003;3(12):921-930.

[DOI]
5. Ng LG, Mrass P, Kinjyo I, Reiner SL, Weninger W. Two-photon imaging of effector T-cell behavior: Lessons from a tumor model. Immunol Rev. 2008;221:147-162.

[DOI] [PubMed]
6. Hickman HD. New insights into antiviral immunity gained through intravital imaging. Curr Opin Virol. 2017;22:59-63.

[DOI] [PubMed]
7. Entenberg D, Oktay MH, Condeelis JS. Intravital imaging to study cancer progression and metastasis. Nat Rev Cancer. 2023;23(1):25-42.

[DOI]
8. Goltsev Y, Samusik N, Kennedy-Darling J, Bhate S, Hale M, Vazquez G, et al. Deep profiling of mouse splenic architecture with CODEX multiplexed imaging. Cell. 2018;174(4):968-981.e15.

[DOI] [PubMed] [PMC]
9. Radtke AJ, Kandov E, Lowekamp B, Speranza E, Chu CJ, Gola A, et al. IBEX: A versatile multiplex optical imaging approach for deep phenotyping and spatial analysis of cells in complex tissues. Proc Natl Acad Sci U S A. 2020;117(52):33455-33465.

[DOI] [PubMed] [PMC]
10. Ng LG, Qin JS, Roediger B, Wang Y, Jain R, Cavanagh LL, et al. Visualizing the neutrophil response to sterile tissue injury in mouse dermis reveals a three-phase cascade of events. J Invest Dermatol. 2011;131(10):2058-2068.

[DOI] [PubMed]
11. Lämmermann T, Afonso PV, Angermann BR, Wang JM, Kastenmüller W, Parent CA, et al. Neutrophil swarms require LTB4 and integrins at sites of cell death in vivo. Nature. 2013;498(7454):371-375.

[DOI] [PubMed] [PMC]
12. Park CO, Kupper TS. The emerging role of resident memory T cells in protective immunity and inflammatory disease. Nat Med. 2015;21(7):688-697.

[DOI] [PubMed] [PMC]
13. Zaid A, MacKay LK, Rahimpour A, Braun A, Veldhoen M, Carbone FR, et al. Persistence of skin-resident memory T cells within an epidermal niche. Proc Natl Acad Sci U S A. 2014;111(14):5307-5312.

[DOI] [PubMed] [PMC]
14. Boissonnas A, Fetler L, Zeelenberg IS, Hugues S, Amigorena S. In vivo imaging of cytotoxic T cell infiltration and elimination of a solid tumor. J Exp Med. 2007;204(2):345-356.

[DOI] [PubMed] [PMC]
15. Breart B, Lemaître F, Celli S, Bousso P. Two-photon imaging of intratumoral CD8⁺ T cell cytotoxic activity during adoptive T cell therapy in mice. J Clin Invest. 2008;118(4):1390-1397.

[DOI] [PubMed] [PMC]
16. Clatworthy MR, Aronin CE, Mathews RJ, Morgan NY, Smith KG, Germain RN. Immune complexes stimulate CCR7-dependent dendritic cell migration to lymph nodes. Nat Med. 2014;20(12):1458-1463.

[DOI] [PubMed] [PMC]
17. Finsterbusch M, Hall P, Li A, Devi S, Westhorpe CL, Kitching AR, et al. Patrolling monocytes promote intravascular neutrophil activation and glomerular injury in the acutely inflamed glomerulus. Proc Natl Acad Sci U S A. 2016;113(35):E5172-E5181.

[DOI] [PubMed] [PMC]
18. Boulch M, Grandjean CL, Cazaux M, Bousso P. Tumor immunosurveillance and immunotherapies: A fresh look from intravital imaging. Trends Immunol. 2019;40(11):1022-1034.

[DOI] [PubMed]
19. Hor JL, Germain RN. Intravital and high-content multiplex imaging of the immune system. Trends Cell Biol. 2022;32(5):406-420.

[DOI] [PubMed] [PMC]
20. Peng X, Wang Y, Zhang J, Zhang Z, Qi S. Intravital imaging of the functions of immune cells in the tumor microenvironment during immunotherapy. Front Immunol. 2023;14:1288273.

[DOI]
21. Geels SN, Moshensky A, Sousa RS, Murat C, Bustos MA, Walker BL, et al. Interruption of the intratumor CD8⁺ T cell: Treg crosstalk improves the efficacy of PD-1 immunotherapy. Cancer Cell. 2024;42(6):1051-1066.e7.

[DOI] [PubMed] [PMC]
22. Chtanova T, Hampton HR, Waterhouse LA, Wood K, Tomura M, Miwa Y, et al. Real-time interactive two-photon photoconversion of recirculating lymphocytes for discontinuous cell tracking in live adult mice. J Biophotonics. 2014;7(6):425-433.

[DOI] [PubMed]
23. Devi S, Alexandre YO, Loi JK, Gillis R, Ghazanfari N, Creed SJ, et al. Adrenergic regulation of the vasculature impairs leukocyte interstitial migration and suppresses immune responses. Immunity. 2021;54(6):1219-1230.e7.

[DOI] [PubMed]
24. Kaszas A, Szalay G, Slézia A, Bojdán A, Vanzetta I, Hangya B, et al. Two-photon GCaMP6f imaging of infrared neural stimulation evoked calcium signals in mouse cortical neurons in vivo. Sci Rep. 2021;11(1):9775.

[DOI] [PubMed] [PMC]
25. Westhorpe CLV, Norman MU, Hall P, Snelgrove SL, Finsterbusch M, Li A, et al. Effector CD4⁺ T cells recognize intravascular antigen presented by patrolling monocytes. Nat Commun. 2018;9(1):747.

[DOI] [PubMed] [PMC]
26. Marangoni F, Murooka TT, Manzo T, Kim EY, Carrizosa E, Elpek NM, et al. The transcription factor NFAT exhibits signal memory during serial T cell interactions with antigen-presenting cells. Immunity. 2013;38(2):237-249.

[DOI] [PubMed] [PMC]
27. Evrard M, Kwok IWH, Chong SZ, Teng KWW, Becht E, Chen J, et al. Developmental analysis of bone marrow neutrophils reveals populations specialized in expansion, trafficking, and effector functions. Immunity. 2018;48(2):364-379.e8.

[DOI] [PubMed]
28. Ng MSF, Kwok I, Tan L, Shi C, Cerezo-Wallis D, Tan Y, et al. Deterministic reprogramming of neutrophils within tumors. Science. 2024;383(6679):eadf6493.

[DOI]
29. Ballesteros I, Hidalgo A. The neutrophil collective. Cell. 2025;188(25):7019-7035.

[DOI]
30. Cerezo-Wallis D, Rubio-Ponce A, Richter M, Pitino E, Kwok I, Marteletto G, et al. Architecture of the neutrophil compartment. Nature. 2026;649(8098):1003-1012.

[DOI]
31. 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.

[PubMed]
32. Schmidt H, Bastholt L, Geertsen P, Christensen IJ, Larsen S, Gehl J, et al. Elevated neutrophil and monocyte counts in peripheral blood are associated with poor survival in patients with metastatic melanoma: A prognostic model. Br J Cancer. 2005;93(3):273-278.

[DOI] [PubMed] [PMC]
33. 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.

[DOI]
34. Trellakis S, Bruderek K, Dumitru CA, Gholaman H, Gu X, Bankfalvi A, 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.

[DOI]
35. 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.

[DOI] [PubMed] [PMC]
36. Nahrendorf M, Swirski FK. Abandoning M1/M2 for a network model of macrophage function. Circ Res. 2016;119(3):414-417.

[DOI] [PubMed] [PMC]
37. Gabrilovich DI, Bronte V, Chen SH, Colombo MP, Ochoa A, Ostrand-Rosenberg S, et al. The terminology issue for myeloid-derived suppressor cells. Cancer Res. 2007;67(1):425.

[DOI]
38. Yang R, Cai Z, Zhang Y, Yutzy WH 4th, Roby KF, Roden RB. CD80 in immune suppression by mouse ovarian carcinoma-associated Gr-1+CD11b+ myeloid cells. Cancer Res. 2006;66(13):6807-6815.

[DOI] [PubMed]
39. Alshetaiwi H, Pervolarakis N, McIntyre LL, Ma D, Nguyen Q, Rath JA, et al. Defining the emergence of myeloid-derived suppressor cells in breast cancer using single-cell transcriptomics. Sci Immunol. 2020;5(44):eaay6017.

[DOI] [PubMed] [PMC]
40. Salcher S, Sturm G, Horvath L, Untergasser G, Kuempers C, Fotakis G, et al. High-resolution single-cell atlas reveals diversity and plasticity of tissue-resident neutrophils in non-small cell lung cancer. Cancer Cell. 2022;40(12):1503-1520.e8.

[DOI] [PubMed] [PMC]
41. Pfirschke C, Engblom C, Gungabeesoon J, Lin Y, Rickelt S, Zilionis R, et al. Tumor-promoting ly-6G⁺ SiglecF^high cells are mature and long-lived neutrophils. Cell Rep. 2020;32(12):108164.

[DOI] [PubMed] [PMC]
42. Zilionis R, Engblom C, Pfirschke C, Savova V, Zemmour D, Saatcioglu HD, et al. Single-cell transcriptomics of human and mouse lung cancers reveals conserved myeloid populations across individuals and species. Immunity. 2019;50(5):1317-1334.e10.

[DOI] [PubMed] [PMC]
43. Veglia F, Hashimoto A, Dweep H, Sanseviero E, de Leo A, Tcyganov E, et al. Analysis of classical neutrophils and polymorphonuclear myeloid-derived suppressor cells in cancer patients and tumor-bearing mice. J Exp Med. 2021;218(4):e20201803.

[DOI] [PubMed] [PMC]
44. Gong Z, Li Q, Shi J, Li P, Hua L, Shultz LD, et al. Immunosuppressive reprogramming of neutrophils by lung mesenchymal cells promotes breast cancer metastasis. Sci Immunol. 2023;8(80):eadd5204.

[DOI]
45. Park SL, Buzzai A, Rautela J, Hor JL, Hochheiser K, Effern M, et al. Tissue-resident memory CD8⁺ T cells promote melanoma-immune equilibrium in skin. Nature. 2019;565(7739):366-371.

[DOI] [PubMed]
46. Manaster Y, Shipony Z, Hutzler A, Kolesnikov M, Avivi C, Shalmon B, et al. Reduced CTL motility and activity in avascular tumor areas. Cancer Immunol Immunother. 2019;68(8):1287-1301.

[DOI] [PubMed] [PMC]
47. Lau D, Garçon F, Chandra A, Lechermann LM, Aloj L, Chilvers ER, et al. Intravital imaging of adoptive T-cell morphology, mobility and trafficking following immune checkpoint inhibition in a mouse melanoma model. Front Immunol. 2020;11:1514.

[DOI]
48. Park I, Hong S, Seok J, Lucia SE, Song E, Kim M, et al. Longitudinal intravital imaging of tumor-infiltrating lymphocyte motility in breast cancer models. J Breast Cancer. 2021;24(5):463-473.

[DOI] [PubMed] [PMC]
49. Mrass P, Takano H, Ng LG, Daxini S, Lasaro MO, Iparraguirre A, et al. Random migration precedes stable target cell interactions of tumor-infiltrating T cells. J Exp Med. 2006;203(12):2749-2761.

[DOI] [PubMed] [PMC]
50. Zhang SW, Wang H, Xiao Y, Liu LT, Shen M, Wang Z, et al. Sensory neurons drive immune exclusion by stimulating a dense extracellular matrix in the breast cancer tumor microenvironment. Cell. 2026;189(4):1039-1055.e20.

[DOI] [PubMed]
51. Bougherara H, Mansuet-Lupo A, Alifano M, Ngô C, Damotte D, Le Frère-Belda MA, et al. Real-time imaging of resident T cells in human lung and ovarian carcinomas reveals how different tumor microenvironments control T lymphocyte migration. Front Immunol. 2015;6:500.

[DOI]
52. Broz ML, Binnewies M, Boldajipour B, Nelson AE, Pollack JL, Erle DJ, et al. Dissecting the tumor myeloid compartment reveals rare activating antigen-presenting cells critical for T cell immunity. Cancer Cell. 2014;26(6):938.

[DOI]
53. Loyher PL, Hamon P, Laviron M, Meghraoui-Kheddar A, Goncalves E, Deng Z, et al. Macrophages of distinct origins contribute to tumor development in the lung. J Exp Med. 2018;215(10):2536-2553.

[DOI] [PubMed] [PMC]
54. Ng M, Cerezo-Wallis D, Ng LG, Hidalgo A. Adaptations of neutrophils in cancer. Immunity. 2025;58(1):40-58.

[DOI]
55. Li JL, Lim CH, Tay FW, Goh CC, Devi S, Malleret B, et al. Neutrophils self-regulate immune complex-mediated cutaneous inflammation through CXCL2. J Invest Dermatol. 2016;136(2):416-424.

[DOI] [PubMed]
56. Devi S, Wang Y, Chew WK, Lima R, A-González N, Mattar CNZ, et al. Neutrophil mobilization via plerixafor-mediated CXCR4 inhibition arises from lung demargination and blockade of neutrophil homing to the bone marrow. J Exp Med. 2013;210(11):2321-2336.

[DOI]
57. Casanova-Acebes M, Nicolás-Ávila JA, Li JL, García-Silva S, Balachander A, Rubio-Ponce A, et al. Neutrophils instruct homeostatic and pathological states in naive tissues. J Exp Med. 2018;215(11):2778-2795.

[DOI] [PubMed] [PMC]
58. Looney MR, Thornton EE, Sen D, Lamm WJ, Glenny RW, Krummel MF. Stabilized imaging of immune surveillance in the mouse lung. Nat Methods. 2011;8(1):91-96.

[DOI] [PubMed] [PMC]
59. McDonald B, Spicer J, Giannais B, Fallavollita L, Brodt P, Ferri LE. Systemic inflammation increases cancer cell adhesion to hepatic sinusoids by neutrophil mediated mechanisms. Int J Cancer. 2009;125(6):1298-1305.

[DOI] [PubMed]
60. Spicer JD, McDonald B, Cools-Lartigue JJ, Chow SC, Giannias B, Kubes P, et al. Neutrophils promote liver metastasis via Mac-1-mediated interactions with circulating tumor cells. Cancer Res. 2012;72(16):3919-3927.

[DOI] [PubMed]
61. Devi S, Li A, Westhorpe CL, Lo CY, Abeynaike LD, Snelgrove SL, et al. Multiphoton imaging reveals a new leukocyte recruitment paradigm in the glomerulus. Nat Med. 2013;19(1):107-112.

[DOI] [PubMed]
62. Faust N, Varas F, Kelly LM, Heck S, Graf T. Insertion of enhanced green fluorescent protein into the lysozyme gene creates mice with green fluorescent granulocytes and macrophages. Blood. 2000;96(2):719-726.

[DOI]
63. Hasenberg A, Hasenberg M, Männ L, Neumann F, Borkenstein L, Stecher M, et al. Catchup: A mouse model for imaging-based tracking and modulation of neutrophil granulocytes. Nat Methods. 2015;12(5):445-452.

[DOI] [PubMed]
64. Cao J, Yaw HP, Yi S, Zhou Y, Qin S, Wang Y, et al. Genetic tool for specific tracking of mature neutrophils. bioRxiv [Preprint]. 2026.

[DOI]
65. Turk M, Naumenko V, Mahoney DJ, Jenne CN. Tracking cell recruitment and behavior within the tumor microenvironment using advanced intravital imaging approaches. Cells. 2018;7(7):69.

[DOI] [PubMed] [PMC]
66. Takeichi T, Engelmann G, Mocevicius P, Schmidt J, Ryschich E. 4-dimensional intravital microscopy: A new model for studies of leukocyte recruitment and migration in hepatocellular cancer in mice. J Gastrointest Surg. 2010;14(5):867-872.

[DOI] [PubMed]
67. Sody S, Uddin M, Grüneboom A, Görgens A, Giebel B, Gunzer M, et al. Distinct spatio-temporal dynamics of tumor-associated neutrophils in small tumor lesions. Front Immunol. 2019;10:1419.

[DOI] [PubMed] [PMC]
68. Yam AO, Bailey J, Lin F, Jakovija A, Youlten SE, Counoupas C, et al. Neutrophil conversion to a tumor-killing phenotype underpins effective microbial therapy. Cancer Res. 2023;83(8):1315-1328.

[DOI] [PubMed] [PMC]
69. Park J, Wysocki RW, Amoozgar Z, Maiorino L, Fein MR, Jorns J, et al. Cancer cells induce metastasis-supporting neutrophil extracellular DNA traps. Sci Transl Med. 2016;8(361):361ra138.

[DOI] [PubMed] [PMC]
70. Teijeira Á, Garasa S, Gato M, Alfaro C, Migueliz I, Cirella A, et al. CXCR1 and CXCR2 chemokine receptor agonists produced by tumors induce neutrophil extracellular traps that interfere with immune cytotoxicity. Immunity. 2020;52(5):856-871.e8.

[DOI] [PubMed]
71. Adrover JM, Han X, Sun L, Fujii T, Sivetz N, Daßler-Plenker J, et al. Neutrophils drive vascular occlusion, tumour necrosis and metastasis. Nature. 2025;645(8080):484-495.

[DOI] [PubMed] [PMC]
72. Bolli E, Wirapati P, Hicham M, Xie Y, Siwicki M, Duval F, et al. CCL3 is produced by aged neutrophils across cancers and promotes tumor growth. Cancer Cell. 2026;44(3):624-640.e12.

[DOI] [PubMed] [PMC]
73. Song M, He J, Pan QZ, Yang J, Zhao J, Zhang YJ, et al. Cancer-associated fibroblast-mediated cellular crosstalk supports hepatocellular carcinoma progression. Hepatology. 2021;73(5):1717-1735.

[DOI] [PubMed]
74. Cheng Y, Li H, Deng Y, Tai Y, Zeng K, Zhang Y, et al. Cancer-associated fibroblasts induce PDL1⁺ neutrophils through the IL6-STAT3 pathway that foster immune suppression in hepatocellular carcinoma. Cell Death Dis. 2018;9(4):422.

[DOI] [PubMed] [PMC]
75. Munir H, Jones JO, Janowitz T, Hoffmann M, Euler M, Martins CP, et al. Stromal-driven and Amyloid β-dependent induction of neutrophil extracellular traps modulates tumor growth. Nat Commun. 2021;12(1):683.

[DOI] [PubMed] [PMC]
76. Szpunar MJ, Belcher EK, Dawes RP, Madden KS. Sympathetic innervation, norepinephrine content, and norepinephrine turnover in orthotopic and spontaneous models of breast cancer. Brain Behav Immun. 2016;53:223-233.

[DOI] [PubMed] [PMC]
77. Magnon C, Hall SJ, Lin J, Xue X, Gerber L, Freedland SJ, et al. Autonomic nerve development contributes to prostate cancer progression. Science. 2013;341(6142):1236361.

[DOI] [PubMed]
78. Zahalka AH, Arnal-Estapé A, Maryanovich M, Nakahara F, Cruz CD, Finley LWS, et al. Adrenergic nerves activate an angio-metabolic switch in prostate cancer. Science. 2017;358(6361):321-326.

[DOI] [PubMed] [PMC]
79. Wei HK, Yu CD, Hu B, Zeng X, Ichise H, Li L, et al. Tumour-brain crosstalk restrains cancer immunity via a sensory-sympathetic axis. Nature. 2026;650:1007-1016.

[DOI]
80. Barr J, Kruse A, Restaino A, Tulina N, Stuckelberger S, Vermeer S, et al. Intra-tumoral nerve-tracing in a novel syngeneic model of high-grade serous ovarian carcinoma. Cells. 2021;10(12):3491.

[DOI]
81. Le TT, Payne SL, Buckwald MN, Hayes LA, Parker SR, Burge CB, et al. Sensory nerves enhance triple-negative breast cancer invasion and metastasis via the axon guidance molecule PlexinB3. NPJ Breast Cancer. 2022;8(1):116.

[DOI] [PubMed] [PMC]
82. Wood JN, Yan N, Huang J, Zhao J, Akopian A, et al. Sensory neuron sodium channels as pain targets; from cocaine to Journavx (VX-548, suzetrigine). J Gen Physiol. 2025;157(4):e202513778.

[DOI]
83. Costa PAC, Silva WN, Prazeres PHDM, Picoli CC, Guardia GDA, Costa AC, et al. Chemogenetic modulation of sensory neurons reveals their regulating role in melanoma progression. Acta Neuropathol Commun. 2021;9(1):183.

[DOI] [PubMed] [PMC]
84. Mueller SN. Neural control of immune cell trafficking. J Exp Med. 2022;219(3):e20211604.

[DOI]
85. Nicholls AJ, Wen SW, Hall P, Hickey MJ, Wong CHY. Activation of the sympathetic nervous system modulates neutrophil function. J Leukoc Biol. 2018;103(2):295-309.

[DOI]
86. Scanzano A, Schembri L, Rasini E, Luini A, Dallatorre J, Legnaro M, et al. Adrenergic modulation of migration, CD11b and CD18 expression, ROS and interleukin-8 production by human polymorphonuclear leukocytes. Inflamm Res. 2015;64(2):127-135.

[DOI] [PubMed]
87. Trabold B, Gruber M, Fröhlich D. Functional and phenotypic changes in polymorphonuclear neutrophils induced by catecholamines. Scand Cardiovasc J. 2007;41(1):59-64.

[DOI]
88. Gosain A, Gamelli RL, DiPietro LA. Norepinephrine-mediated suppression of phagocytosis by wound neutrophils. J Surg Res. 2009;152(2):311-318.

[DOI] [PubMed] [PMC]
89. Kim MH, Gorouhi F, Ramirez S, Granick JL, Byrne BA, Soulika AM, et al. Catecholamine stress alters neutrophil trafficking and impairs wound healing by β2-adrenergic receptor-mediated upregulation of IL-6. J Invest Dermatol. 2014;134(3):809-817.

[DOI] [PubMed] [PMC]
90. Ao T, Kikuta J, Sudo T, Uchida Y, Kobayashi K, Ishii M. Local sympathetic neurons promote neutrophil egress from the bone marrow at the onset of acute inflammation. Int Immunol. 2020;32(11):727-736.

[DOI] [PubMed]
91. Ochoa MC, Sanchez-Gregorio S, de Andrea CE, Garasa S, Alvarez M, Olivera I, et al. Synergistic effects of combined immunotherapy strategies in a model of multifocal hepatocellular carcinoma. Cell Rep Med. 2023;4(4):101009.

[DOI]
92. Highfill SL, Cui Y, Giles AJ, Smith JP, Zhang H, Morse E, et al. Disruption of CXCR2-mediated MDSC tumor trafficking enhances anti-PD1 efficacy. Sci Transl Med. 2014;6(237):237ra67.

[DOI] [PubMed] [PMC]
93. Kwak JW, Nguyen HQ, Camai A, Huffman GM, Mekvanich S, Kenney NN, et al. CXCR1/2 antagonism inhibits neutrophil function and not recruitment in cancer. OncoImmunology. 2024;13(1):2384674.

[DOI]
94. Kargl J, Zhu X, Zhang H, Yang GHY, Friesen TJ, Shipley M, et al. Neutrophil content predicts lymphocyte depletion and anti-PD1 treatment failure in NSCLC. JCI Insight. 2019;4(24):e130850.

[DOI] [PubMed] [PMC]
95. Clavijo PE, Moore EC, Chen J, Davis RJ, Friedman J, Kim Y, et al. Resistance to CTLA-4 checkpoint inhibition reversed through selective elimination of granulocytic myeloid cells. Oncotarget. 2017;8(34):55804-55820.

[DOI] [PubMed] [PMC]
96. Steele CW, Karim SA, Leach JDG, Bailey P, Upstill-Goddard R, Rishi L, et al. CXCR2 inhibition profoundly suppresses metastases and augments immunotherapy in pancreatic ductal adenocarcinoma. Cancer Cell. 2016;29(6):832-845.

[DOI] [PubMed] [PMC]
97. Sun L, Clavijo PE, Robbins Y, Patel P, Friedman J, Greene S, et al. Inhibiting myeloid-derived suppressor cell trafficking enhances T cell immunotherapy. JCI Insight. 2019;4(7):e126853.

[DOI]
98. Pei S, Pan Y, Liang H, Lei L, Lin Q, Mi J, et al. Neutrophil regulation of immunotherapy for cancer is controlled by type II interferon. Immunity. 2026.

[DOI]
99. Kalafati L, Kourtzelis I, Schulte-Schrepping J, Li X, Hatzioannou A, Grinenko T, et al. Innate immune training of granulopoiesis promotes anti-tumor activity. Cell. 2020;183(3):771-785.e12.

[DOI] [PubMed] [PMC]
100. Mohammadpour H, MacDonald CR, Qiao G, Chen M, Dong B, Hylander BL, et al. β2 adrenergic receptor-mediated signaling regulates the immunosuppressive potential of myeloid-derived suppressor cells. J Clin Invest. 2019;129(12):5537-5552.

[DOI] [PubMed] [PMC]

Copyright

© The Author(s) 2026. This is an Open Access article licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Publisher’s Note

Science Exploration remains a neutral stance on jurisdictional claims in published maps and institutional affiliations. The views expressed in this article are solely those of the author(s) and do not reflect the opinions of the Editors or the publisher.