dc.contributor.author | Eisenblaetter, M | |
dc.contributor.author | Flores-Borja, F | |
dc.contributor.author | Lee, JJ | |
dc.contributor.author | Wefers, C | |
dc.contributor.author | Smith, H | |
dc.contributor.author | Hueting, R | |
dc.contributor.author | Cooper, MS | |
dc.contributor.author | Blower, PJ | |
dc.contributor.author | Patel, D | |
dc.contributor.author | Rodriguez-Justo, M | |
dc.contributor.author | Milewicz, H | |
dc.contributor.author | Vogl, T | |
dc.contributor.author | Roth, J | |
dc.contributor.author | Tutt, A | |
dc.contributor.author | Schaeffter, T | |
dc.contributor.author | Ng, T | |
dc.date.accessioned | 2018-01-24T10:34:46Z | |
dc.date.issued | 2017-06-15 | |
dc.identifier.citation | Theranostics, 2017, 7 (9), pp. 2392 - 2401 | |
dc.identifier.issn | 1838-7640 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/1006 | |
dc.identifier.eissn | 1838-7640 | |
dc.identifier.doi | 10.7150/thno.17138 | |
dc.description.abstract | Background 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. Methods 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. Results 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). Conclusion We report S100A8/A9 as a potent imaging biomarker for tumor-mediated immune remodeling with potential applications in basic research and clinical oncology. | |
dc.format | Electronic-eCollection | |
dc.format.extent | 2392 - 2401 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | IVYSPRING INT PUBL | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Animals | |
dc.subject | Mice, Inbred BALB C | |
dc.subject | Breast Neoplasms | |
dc.subject | Lung Neoplasms | |
dc.subject | Neoplasm Metastasis | |
dc.subject | Disease Models, Animal | |
dc.subject | Calgranulin A | |
dc.subject | Calgranulin B | |
dc.subject | Tomography, Emission-Computed, Single-Photon | |
dc.subject | Microscopy, Confocal | |
dc.subject | Flow Cytometry | |
dc.title | Visualization of Tumor-Immune Interaction - Target-Specific Imaging of S100A8/A9 Reveals Pre-Metastatic Niche Establishment. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2017-02-20 | |
rioxxterms.versionofrecord | 10.7150/thno.17138 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2017-01 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Theranostics | |
pubs.issue | 9 | |
pubs.notes | Not known | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR | |
pubs.publication-status | Published | |
pubs.volume | 7 | |
pubs.embargo.terms | Not known | |
dc.contributor.icrauthor | Tutt, Andrew | |