Visualization of tumor-immune interaction - target-specific imaging of S100A8/A9 reveals pre-metastatic niche establishment
<strong>Background</strong> Systemic cancer spread is preceded by the establishment of a permissive microenvironment in the target tissue of metastasis – the premetastatic niche. As crucial players in establishment of the pre-metastatic niche, myeloid derived suppressor cells (MDSC) rele...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Ivyspring International
2017
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| _version_ | 1797098784031768576 |
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| author | Eisenblaetter, M Flores-Borja, F Lee, JJ Wefers, C Smith, H Hueting, R Cooper, MS Blower, PJ Patel, D Rodriguez-Justo, M Milewicz, H Vogl, T Roth, J Tutt, A Schaeffter, T Ng, T |
| author_facet | Eisenblaetter, M Flores-Borja, F Lee, JJ Wefers, C Smith, H Hueting, R Cooper, MS Blower, PJ Patel, D Rodriguez-Justo, M Milewicz, H Vogl, T Roth, J Tutt, A Schaeffter, T Ng, T |
| author_sort | Eisenblaetter, M |
| collection | OXFORD |
| description | <strong>Background</strong> Systemic cancer spread is preceded by the establishment of a permissive microenvironment in the target tissue of metastasis – the premetastatic niche. As crucial players in establishment of the pre-metastatic niche, myeloid derived suppressor cells (MDSC) release S100A8/A9, an exosomal protein that contributes to metastasis, angiogenesis, and immune suppression. We report the application of antibody-based single-photon emission computed tomography (SPECT) for detection of S100A8/A9 in vivo as an imaging marker for pre-metastatic tissue priming. <strong>Methods</strong> A syngeneic model system for invasive breast cancer with (4T1.2) or without (67NR) the tendency to form lung metastasis was established in BALB/c mice. A SPECT-probe has been generated and tested for visualization of S100A9 release. Tumor-associated changes in numbers and fuction of immune cells in pre-metastatic tissue were evaluated by flow cytometry and confocal microscopy. <strong>Results</strong> S100A8/A9 imaging reflected MDSC abundance and the establishment of an immunosuppressive environment in pre-metastatic lung tissue (activity 4T1.2 vs. healthy control: 0.95 vs. 0.45 %ID; p<0.001). The S100A8/A9 imaging signal in the pre-metastatic lung correlated with the subsequent metastatic tumor burden in the same organ (r2=0.788; p<0.0001). CCL2 blockade and the consecutive inhibition of premetastatic niche establishment was clearly depicted by S100A9-SPECT (lung activity untreated vs. treated: 2 vs, 1.4 %ID). <strong>Conclusion</strong> We report S100A8/A9 as a potent imaging biomarker for tumor-mediated immune remodeling with potential applications in basic research and clinical oncology. |
| first_indexed | 2024-03-07T05:14:36Z |
| format | Journal article |
| id | oxford-uuid:dcbf681a-1f98-47d2-9911-d78cbffe59fb |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:14:36Z |
| publishDate | 2017 |
| publisher | Ivyspring International |
| record_format | dspace |
| spelling | oxford-uuid:dcbf681a-1f98-47d2-9911-d78cbffe59fb2022-03-27T09:19:48ZVisualization of tumor-immune interaction - target-specific imaging of S100A8/A9 reveals pre-metastatic niche establishmentJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:dcbf681a-1f98-47d2-9911-d78cbffe59fbEnglishSymplectic Elements at OxfordIvyspring International2017Eisenblaetter, MFlores-Borja, FLee, JJWefers, CSmith, HHueting, RCooper, MSBlower, PJPatel, DRodriguez-Justo, MMilewicz, HVogl, TRoth, JTutt, ASchaeffter, TNg, T<strong>Background</strong> Systemic cancer spread is preceded by the establishment of a permissive microenvironment in the target tissue of metastasis – the premetastatic niche. As crucial players in establishment of the pre-metastatic niche, myeloid derived suppressor cells (MDSC) release S100A8/A9, an exosomal protein that contributes to metastasis, angiogenesis, and immune suppression. We report the application of antibody-based single-photon emission computed tomography (SPECT) for detection of S100A8/A9 in vivo as an imaging marker for pre-metastatic tissue priming. <strong>Methods</strong> A syngeneic model system for invasive breast cancer with (4T1.2) or without (67NR) the tendency to form lung metastasis was established in BALB/c mice. A SPECT-probe has been generated and tested for visualization of S100A9 release. Tumor-associated changes in numbers and fuction of immune cells in pre-metastatic tissue were evaluated by flow cytometry and confocal microscopy. <strong>Results</strong> S100A8/A9 imaging reflected MDSC abundance and the establishment of an immunosuppressive environment in pre-metastatic lung tissue (activity 4T1.2 vs. healthy control: 0.95 vs. 0.45 %ID; p<0.001). The S100A8/A9 imaging signal in the pre-metastatic lung correlated with the subsequent metastatic tumor burden in the same organ (r2=0.788; p<0.0001). CCL2 blockade and the consecutive inhibition of premetastatic niche establishment was clearly depicted by S100A9-SPECT (lung activity untreated vs. treated: 2 vs, 1.4 %ID). <strong>Conclusion</strong> We report S100A8/A9 as a potent imaging biomarker for tumor-mediated immune remodeling with potential applications in basic research and clinical oncology. |
| spellingShingle | Eisenblaetter, M Flores-Borja, F Lee, JJ Wefers, C Smith, H Hueting, R Cooper, MS Blower, PJ Patel, D Rodriguez-Justo, M Milewicz, H Vogl, T Roth, J Tutt, A Schaeffter, T Ng, T Visualization of tumor-immune interaction - target-specific imaging of S100A8/A9 reveals pre-metastatic niche establishment |
| title | Visualization of tumor-immune interaction - target-specific imaging of S100A8/A9 reveals pre-metastatic niche establishment |
| title_full | Visualization of tumor-immune interaction - target-specific imaging of S100A8/A9 reveals pre-metastatic niche establishment |
| title_fullStr | Visualization of tumor-immune interaction - target-specific imaging of S100A8/A9 reveals pre-metastatic niche establishment |
| title_full_unstemmed | Visualization of tumor-immune interaction - target-specific imaging of S100A8/A9 reveals pre-metastatic niche establishment |
| title_short | Visualization of tumor-immune interaction - target-specific imaging of S100A8/A9 reveals pre-metastatic niche establishment |
| title_sort | visualization of tumor immune interaction target specific imaging of s100a8 a9 reveals pre metastatic niche establishment |
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