In vivo imaging of microenvironmental and anti-PD-L1-mediated dynamics in cancer using S100A8/S100A9 as an imaging biomarker
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In vivo imaging of microenvironmental and anti-PD-L1-mediated dynamics in cancer using S100A8/S100A9 as an imaging biomarker. / Helfen, Anne; Rieß, Jan; Fehler, Olesja; Stölting, Miriam; An, Zhengwen; Kocman, Vanessa; Schnepel, Annika; Geyer, Christiane; Gerwing, Mirjam; Masthoff, Max; Vogl, Thomas; Höltke, Carsten; Roth, Johannes; Ng, Tony; Wildgruber, Moritz; Eisenblätter, Michel.
in: NEOPLASIA, Jahrgang 28, 100792, 06.2022.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - In vivo imaging of microenvironmental and anti-PD-L1-mediated dynamics in cancer using S100A8/S100A9 as an imaging biomarker
AU - Helfen, Anne
AU - Rieß, Jan
AU - Fehler, Olesja
AU - Stölting, Miriam
AU - An, Zhengwen
AU - Kocman, Vanessa
AU - Schnepel, Annika
AU - Geyer, Christiane
AU - Gerwing, Mirjam
AU - Masthoff, Max
AU - Vogl, Thomas
AU - Höltke, Carsten
AU - Roth, Johannes
AU - Ng, Tony
AU - Wildgruber, Moritz
AU - Eisenblätter, Michel
N1 - Copyright © 2022. Published by Elsevier Inc.
PY - 2022/6
Y1 - 2022/6
N2 - PURPOSE: As a promotor of tumor invasion and tumor microenvironment (TME) formation, the protein complex S100A8/S100A9 is associated with poor prognosis. Our aim was to further evaluate its origin and regulatory effects, and to establish an imaging biomarker for TME activity.METHODS: S100A9-/-cells (ko) were created from syngeneic murine breast cancer 4T1 (high malignancy) and 67NR (low malignancy) wildtype (wt) cell lines and implanted into either female BALB/c wildtype or S100A9-/- mice (n = 10 each). Anti-S100A9-Cy5.5-targeted fluorescence reflectance imaging was performed at 0 h and 24 h after injection. Potential early changes of S100A9-presence under immune checkpoint inhibition (anti-PD-L1, n = 7 vs. rat IgG2b as isotype control, n = 3) were evaluated.RESULTS: In S100A9-/-mice contrast-to-noise-ratios were significantly reduced for wt and S100A9-/-tumors. No significant differences were detected for 4T1 ko and 67NR ko cells as compared to wildtype cells. Under anti-PD-L1 treatment S100A9 presence significantly decreased compared with the control group.CONCLUSION: Our results confirm a secretion of S100A8/S100A9 by the TME, while tumor cells do not apparently release the protein. Under immune checkpoint inhibition S100A9-imaging reports an early decrease of TME activity. Therefore, S100A9-specific imaging may serve as an imaging biomarker for TME formation and activity.
AB - PURPOSE: As a promotor of tumor invasion and tumor microenvironment (TME) formation, the protein complex S100A8/S100A9 is associated with poor prognosis. Our aim was to further evaluate its origin and regulatory effects, and to establish an imaging biomarker for TME activity.METHODS: S100A9-/-cells (ko) were created from syngeneic murine breast cancer 4T1 (high malignancy) and 67NR (low malignancy) wildtype (wt) cell lines and implanted into either female BALB/c wildtype or S100A9-/- mice (n = 10 each). Anti-S100A9-Cy5.5-targeted fluorescence reflectance imaging was performed at 0 h and 24 h after injection. Potential early changes of S100A9-presence under immune checkpoint inhibition (anti-PD-L1, n = 7 vs. rat IgG2b as isotype control, n = 3) were evaluated.RESULTS: In S100A9-/-mice contrast-to-noise-ratios were significantly reduced for wt and S100A9-/-tumors. No significant differences were detected for 4T1 ko and 67NR ko cells as compared to wildtype cells. Under anti-PD-L1 treatment S100A9 presence significantly decreased compared with the control group.CONCLUSION: Our results confirm a secretion of S100A8/S100A9 by the TME, while tumor cells do not apparently release the protein. Under immune checkpoint inhibition S100A9-imaging reports an early decrease of TME activity. Therefore, S100A9-specific imaging may serve as an imaging biomarker for TME formation and activity.
KW - Animals
KW - Biomarkers
KW - Breast Neoplasms/metabolism
KW - Calgranulin A/genetics
KW - Calgranulin B/genetics
KW - Female
KW - Humans
KW - Immune Checkpoint Inhibitors
KW - Mice
KW - Rats
KW - Tumor Microenvironment
U2 - 10.1016/j.neo.2022.100792
DO - 10.1016/j.neo.2022.100792
M3 - SCORING: Journal article
C2 - 35367789
VL - 28
JO - NEOPLASIA
JF - NEOPLASIA
SN - 1476-5586
M1 - 100792
ER -