Visualization of tumor-immune interaction: Target-specific imaging of S100A8/A9 reveals pre-metastatic niche establishment

Michel Eisenblaetter*, Fabian Flores-Borja, Jae Jin Lee, Christina Wefers, Hannah Smith, Rebekka Hueting, Margaret Susan Cooper, Philip J Blower, Dominic Patel, Manuel Rodriguez-Justo, Hanna Milewicz, Thomas Vogl, Johannes Roth, Andrew Tutt, Tobias Schaeffter, Tony Ng

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

95 Citations (Scopus)
209 Downloads (Pure)

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.

Original languageEnglish
Pages (from-to)2392-2401
JournalTheranostics
Volume7
Issue number9
Early online date15 Jun 2017
DOIs
Publication statusPublished - 31 Aug 2017

Keywords

  • Imaging
  • MDSC
  • Premetastatic niche
  • Tumour immunology

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