Phototheranostics of Splenic Myeloid-Derived Suppressor Cells and Its Impact on Spleen Metabolism in Tumor-Bearing Mice

James D Barnett; Jiefu Jin; Marie-France Penet; Hisataka Kobayashi; Zaver M Bhujwalla

doi:10.3390/cancers14153578

Phototheranostics of Splenic Myeloid-Derived Suppressor Cells and Its Impact on Spleen Metabolism in Tumor-Bearing Mice

Cancers (Basel). 2022 Jul 22;14(15):3578. doi: 10.3390/cancers14153578.

Authors

James D Barnett¹, Jiefu Jin¹, Marie-France Penet^{1

2}, Hisataka Kobayashi³, Zaver M Bhujwalla^{1

2

4}

Affiliations

¹ Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
² Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
³ Molecular Imaging Branch, Center for Cancer Research, National Cancer Institute, US National Institutes of Health, Bethesda, MD 20814, USA.
⁴ Department of Radiation Oncology and Molecular Radiation Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Abstract

(1) Background: MDSCs play an active role in the immune surveillance escape of cancer cells. Because MDSCs in mice are CD11b⁺Gr1⁺, near-infrared photoimmunotherapy (NIR-PIT) using the NIR dye IR700 conjugated to an MDSC-binding antibody provides an opportunity for targeted elimination of MDSCs. (2) Methods: The efficacy of Gr1-IR700-mediated NIR-PIT was evaluated in vitro using magnetically separated CD11b⁺Gr1⁺ MDSCs from spleens of 4T1-luc tumor-bearing (TB) mice. For in vivo evaluation, spleens of Gr1-IR700-injected 4T1-luc TB mice were irradiated with NIR light, and splenocyte viability was determined using CCK-8 assays. Metabolic profiling of NIR-PIT-irradiated spleens was performed using ¹H MRS. (3) Results: Flow cytometric analysis confirmed a ten-fold increase in splenic MDSCs in 4T1-luc TB mice. Gr1-IR700-mediated NIR-PIT eliminated tumor-induced splenic MDSCs in culture. Ex vivo fluorescence imaging revealed an 8- and 9-fold increase in mean fluorescence intensity (MFI) in the spleen and lungs of Gr1-IR700-injected compared to IgG-IR700-injected TB mice. Splenocytes from Gr1-IR700-injected TB mice exposed in vivo to NIR-PIT demonstrated significantly lower viability compared to no light exposure or untreated control groups. Significant metabolic changes were observed in spleens following NIR-PIT. (4) Conclusions: Our data confirm the ability of NIR-PIT to eliminate splenic MDSCs, identifying its potential to eliminate MDSCs in tumors to reduce immune suppression. The metabolic changes observed may identify potential biomarkers of splenic MDSC depletion as well as potential metabolic targets of MDSCs.

Keywords: MDSCs; cancer; metabolism; photoimmunotherapy; spleen.

Abstract

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