Anne Becker1, Nils Große Hokamp1, Stefanie Zenker2, Fabian Flores-Borja3, Katarzyna Barzcyk2, Georg Varga4, Johannes Roth5, Christiane Geyer6, Walter Heindel1, Christoph Bremer7, Thomas Vogl5, Michel Eisenblaetter8. 1. Department of Clinical Radiology, University Hospital Münster, Münster, Germany. 2. Institute of Immunology, University Hospital Münster, Münster, Germany. 3. Richard Dimbleby Department of Cancer Research, King's College London, London, United Kingdom Breakthrough Breastcancer Unit, Guy's and St. Thomas' NHS Hospital Trust, London, United Kingdom. 4. Department of Paediatric Rheumatology and Immunology, University Hospital Münster, Münster, Germany. 5. Institute of Immunology, University Hospital Münster, Münster, Germany Interdisciplinary Center for Clinical Research, Münster University, Münster, Germany. 6. Department of Clinical Radiology, University Hospital Münster, Münster, Germany Interdisciplinary Center for Clinical Research, Münster University, Münster, Germany. 7. Interdisciplinary Center for Clinical Research, Münster University, Münster, Germany Department of Radiology, St. Franziskus Hospital GmbH Münster, Münster, Germany; and. 8. Department of Clinical Radiology, University Hospital Münster, Münster, Germany Richard Dimbleby Department of Cancer Research, King's College London, London, United Kingdom Division of Imaging Sciences and Biomedical Engineering, King's College London, London, United Kingdom michel.eisenblaetter@kcl.ac.uk.
Abstract
UNLABELLED: Tumors recruit and reprogram immune cells to support tumor development and spread, the most prominent among them being of monocytic origin such as tumor-associated macrophages (TAM) or myeloid-derived suppressor cells (MDSC). The alarmin S100A8/A9 has been implicated in the induction of TAM and MDSC. We assessed S100A9 as a molecular imaging marker for the activity of tumor-associated immune cells in a syngeneic murine breast cancer model. S100A9 could serve as a surrogate marker for tumor immune crosstalk as a function of malignancy, providing a tool with the potential for both basic research in tumor immunology and clinical stratification of patients. METHODS: BALB/c mice were inoculated with murine breast cancer cells of common origin but different metastatic capability. At different times during tumor development, optical imaging was performed using a S100A9-specific probe to visualize activated monocytes. To further explore the impact of tumor-educated monocytes, splenic myeloid cells were isolated from either healthy or tumor-bearing animals and injected into tumor-bearing mice. We analyzed the effect of the cell transfer on immune cell activity and tumor development. RESULTS: We could prove S100A9-driven imaging to sensitively and specifically reflect monocyte activity in primary tumor lesions. The imaging results were corroborated by histology and fluorescence-activated cell sorting analyses. In a prospective experiment, S100A9 imaging proved indicative of the individual tumor growth, with excellent correlation. Moreover, we could show that the monocyte activity as depicted by S100A9 activity in the primary tumor lesion mirrored the tumor's metastatic behavior. Treatment with tumor-primed splenic monocytes induced increased tumor growth, accompanied by an augmented infiltration of activated myeloid cells (MDSC and TAM) into the tumor. The consecutive S100A9 expression as depicted by in vivo imaging was significantly increased. CONCLUSION: S100A9 proved to be a sensitive and specific marker for the activity of tumor-associated immune cells. To our knowledge, S100A9 imaging represents a first in vivo imaging approach for the estimation of recruitment and activity of tumor-associated myeloid immune cells. We demonstrated the potential value of this imaging approach for prediction of local and systemic tumor development.
UNLABELLED: Tumors recruit and reprogram immune cells to support tumor development and spread, the most prominent among them being of monocytic origin such as tumor-associated macrophages (TAM) or myeloid-derived suppressor cells (MDSC). The alarmin S100A8/A9 has been implicated in the induction of TAM and MDSC. We assessed S100A9 as a molecular imaging marker for the activity of tumor-associated immune cells in a syngeneic murine breast cancer model. S100A9 could serve as a surrogate marker for tumor immune crosstalk as a function of malignancy, providing a tool with the potential for both basic research in tumor immunology and clinical stratification of patients. METHODS: BALB/c mice were inoculated with murine breast cancer cells of common origin but different metastatic capability. At different times during tumor development, optical imaging was performed using a S100A9-specific probe to visualize activated monocytes. To further explore the impact of tumor-educated monocytes, splenic myeloid cells were isolated from either healthy or tumor-bearing animals and injected into tumor-bearing mice. We analyzed the effect of the cell transfer on immune cell activity and tumor development. RESULTS: We could prove S100A9-driven imaging to sensitively and specifically reflect monocyte activity in primary tumor lesions. The imaging results were corroborated by histology and fluorescence-activated cell sorting analyses. In a prospective experiment, S100A9 imaging proved indicative of the individual tumor growth, with excellent correlation. Moreover, we could show that the monocyte activity as depicted by S100A9 activity in the primary tumor lesion mirrored the tumor's metastatic behavior. Treatment with tumor-primed splenic monocytes induced increased tumor growth, accompanied by an augmented infiltration of activated myeloid cells (MDSC and TAM) into the tumor. The consecutive S100A9 expression as depicted by in vivo imaging was significantly increased. CONCLUSION: S100A9 proved to be a sensitive and specific marker for the activity of tumor-associated immune cells. To our knowledge, S100A9 imaging represents a first in vivo imaging approach for the estimation of recruitment and activity of tumor-associated myeloid immune cells. We demonstrated the potential value of this imaging approach for prediction of local and systemic tumor development.
Authors: Tom Völler; Andreas Faust; Johannes Roth; Michael Schäfers; Thomas Vogl; Sven Hermann Journal: Mol Imaging Biol Date: 2018-06 Impact factor: 3.488
Authors: Anne Becker; Max Masthoff; Jing Claussen; Steven James Ford; Wolfgang Roll; Matthias Burg; Peter J Barth; Walter Heindel; Michael Schäfers; Michel Eisenblätter; Moritz Wildgruber Journal: Eur Radiol Date: 2017-08-07 Impact factor: 5.315
Authors: Anne Helfen; Nils Große Hokamp; Christiane Geyer; Walter Heindel; Christoph Bremer; Thomas Vogl; Carsten Höltke; Max Masthoff; Katarzyna Barczyk-Kahlert; Johannes Roth; Moritz Wildgruber; Michel Eisenblaetter Journal: Mol Imaging Biol Date: 2020-02 Impact factor: 3.488
Authors: Robert S Oakes; Grace G Bushnell; Sophia M Orbach; Pridvi Kandagatla; Yining Zhang; Aaron H Morris; Matthew S Hall; Petrina LaFaire; Joseph T Decker; Rachel M Hartfield; Michael D Brooks; Max S Wicha; Jacqueline S Jeruss; Lonnie D Shea Journal: Cancer Res Date: 2019-10-29 Impact factor: 12.701
Authors: Michel Eisenblaetter; Fabian Flores-Borja; Jae Jin Lee; Christina Wefers; Hannah Smith; Rebekka Hueting; Margaret S Cooper; Philip J Blower; Dominic Patel; Manuel Rodriguez-Justo; Hanna Milewicz; Thomas Vogl; Johannes Roth; Andrew Tutt; Tobias Schaeffter; Tony Ng Journal: Theranostics Date: 2017-06-15 Impact factor: 11.556
Authors: Ali Khammanivong; Brent S Sorenson; Karen F Ross; Erin B Dickerson; Rifat Hasina; Mark W Lingen; Mark C Herzberg Journal: Oncotarget Date: 2016-03-22