Distinct Spatio-Temporal Dynamics of Tumor-Associated Neutrophils in Small Tumor Lesions
Across a majority of cancer types tumor-associated neutrophils (TAN) are linked with poor prognosis. However, the underlying mechanisms, especially the intratumoral behavior of TAN, are largely unknown. Using intravital multiphoton imaging on a mouse model with neutrophil-specific fluorescence, we m...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2019-06-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.01419/full |
| _version_ | 1818308641112981504 |
|---|---|
| author | Simon Sody Mohib Uddin Anika Grüneboom André Görgens André Görgens Bernd Giebel Matthias Gunzer Sven Brandau |
| author_facet | Simon Sody Mohib Uddin Anika Grüneboom André Görgens André Görgens Bernd Giebel Matthias Gunzer Sven Brandau |
| author_sort | Simon Sody |
| collection | DOAJ |
| description | Across a majority of cancer types tumor-associated neutrophils (TAN) are linked with poor prognosis. However, the underlying mechanisms, especially the intratumoral behavior of TAN, are largely unknown. Using intravital multiphoton imaging on a mouse model with neutrophil-specific fluorescence, we measured the migration of TAN in distinct compartments of solid tumor cell lesions in vivo. By longitudinally quantifying the infiltration and persistence of TAN into growing tumors in the same animals, we observed cells that either populated the peripheral stromal zone of the tumor (peritumoral TAN) or infiltrated into the tumor core (intratumoral TAN). Intratumoral TAN showed prolonged tumor-associated persistence and reduced motility compared to peritumoral TAN, whose velocity increased with tumor progression. Selective pharmacological blockade of CXCR2 receptors using AZD5069 profoundly inhibited recruitment of TAN into peritumoral regions, while intratumoral infiltration was only transiently attenuated and rebounded at later time points. Our findings unravel distinct spatial dynamics of TAN that are partially and differentially regulated via the CXCR2 signaling pathway. |
| first_indexed | 2024-12-13T07:17:30Z |
| format | Article |
| id | doaj.art-4ddc6ed2775645cfb23be24b5e0560b0 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-13T07:17:30Z |
| publishDate | 2019-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-4ddc6ed2775645cfb23be24b5e0560b02022-12-21T23:55:31ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-06-011010.3389/fimmu.2019.01419449512Distinct Spatio-Temporal Dynamics of Tumor-Associated Neutrophils in Small Tumor LesionsSimon Sody0Mohib Uddin1Anika Grüneboom2André Görgens3André Görgens4Bernd Giebel5Matthias Gunzer6Sven Brandau7Department of Otorhinolaryngology, University Hospital Essen, University Duisburg-Essen, Essen, GermanyRespiratory Global Medicines Development (GMD), AstraZeneca, Gothenburg, SwedenInstitute for Experimental Immunology and Imaging, University Hospital Essen, University Duisburg-Essen, Essen, GermanyInstitute for Transfusion Medicine, University Hospital Essen, University Duisburg-Essen, Essen, GermanyDepartment of Laboratory Medicine, Karolinska Institutet, Stockholm, SwedenInstitute for Transfusion Medicine, University Hospital Essen, University Duisburg-Essen, Essen, GermanyInstitute for Experimental Immunology and Imaging, University Hospital Essen, University Duisburg-Essen, Essen, GermanyDepartment of Otorhinolaryngology, University Hospital Essen, University Duisburg-Essen, Essen, GermanyAcross a majority of cancer types tumor-associated neutrophils (TAN) are linked with poor prognosis. However, the underlying mechanisms, especially the intratumoral behavior of TAN, are largely unknown. Using intravital multiphoton imaging on a mouse model with neutrophil-specific fluorescence, we measured the migration of TAN in distinct compartments of solid tumor cell lesions in vivo. By longitudinally quantifying the infiltration and persistence of TAN into growing tumors in the same animals, we observed cells that either populated the peripheral stromal zone of the tumor (peritumoral TAN) or infiltrated into the tumor core (intratumoral TAN). Intratumoral TAN showed prolonged tumor-associated persistence and reduced motility compared to peritumoral TAN, whose velocity increased with tumor progression. Selective pharmacological blockade of CXCR2 receptors using AZD5069 profoundly inhibited recruitment of TAN into peritumoral regions, while intratumoral infiltration was only transiently attenuated and rebounded at later time points. Our findings unravel distinct spatial dynamics of TAN that are partially and differentially regulated via the CXCR2 signaling pathway.https://www.frontiersin.org/article/10.3389/fimmu.2019.01419/fulltumor-associated neutrophilsneutrophil granulocytesintravital imagingmultiphoton microscopytumor microenvironmenttumor immunology |
| spellingShingle | Simon Sody Mohib Uddin Anika Grüneboom André Görgens André Görgens Bernd Giebel Matthias Gunzer Sven Brandau Distinct Spatio-Temporal Dynamics of Tumor-Associated Neutrophils in Small Tumor Lesions Frontiers in Immunology tumor-associated neutrophils neutrophil granulocytes intravital imaging multiphoton microscopy tumor microenvironment tumor immunology |
| title | Distinct Spatio-Temporal Dynamics of Tumor-Associated Neutrophils in Small Tumor Lesions |
| title_full | Distinct Spatio-Temporal Dynamics of Tumor-Associated Neutrophils in Small Tumor Lesions |
| title_fullStr | Distinct Spatio-Temporal Dynamics of Tumor-Associated Neutrophils in Small Tumor Lesions |
| title_full_unstemmed | Distinct Spatio-Temporal Dynamics of Tumor-Associated Neutrophils in Small Tumor Lesions |
| title_short | Distinct Spatio-Temporal Dynamics of Tumor-Associated Neutrophils in Small Tumor Lesions |
| title_sort | distinct spatio temporal dynamics of tumor associated neutrophils in small tumor lesions |
| topic | tumor-associated neutrophils neutrophil granulocytes intravital imaging multiphoton microscopy tumor microenvironment tumor immunology |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.01419/full |
| work_keys_str_mv | AT simonsody distinctspatiotemporaldynamicsoftumorassociatedneutrophilsinsmalltumorlesions AT mohibuddin distinctspatiotemporaldynamicsoftumorassociatedneutrophilsinsmalltumorlesions AT anikagruneboom distinctspatiotemporaldynamicsoftumorassociatedneutrophilsinsmalltumorlesions AT andregorgens distinctspatiotemporaldynamicsoftumorassociatedneutrophilsinsmalltumorlesions AT andregorgens distinctspatiotemporaldynamicsoftumorassociatedneutrophilsinsmalltumorlesions AT berndgiebel distinctspatiotemporaldynamicsoftumorassociatedneutrophilsinsmalltumorlesions AT matthiasgunzer distinctspatiotemporaldynamicsoftumorassociatedneutrophilsinsmalltumorlesions AT svenbrandau distinctspatiotemporaldynamicsoftumorassociatedneutrophilsinsmalltumorlesions |