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Abstract #3020

Investigating the role of the spleen in promoting metabolic, physiological and redox adaptations that drive cancer progression

James D Barnett1, Marie-France Penet2, Raj Kumar Sharma1, Saleem Yousf1, Yelena Mironchik1, Balaji Krishnamachary1, and Zaver M Bhujwalla3
1Division of Cancer Imaging Research, The Johns Hopkins University School of Medicine, Baltimore, MD, United States, 2Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, United States, 3Department of Radiation Oncology and Molecular Radiation Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD, United States

Synopsis

Keywords: Probes & Targets, Cancer

Motivation: We must pave new avenues for cancer treatment by interrogating the pro-tumorigenic properties of the tumor macroenvironment.

Goal(s): We investigate how tumorigenesis metabolically impacts the spleen microenvironment and how the spleen contributes towards cancer progression and resistance.

Approach: Proton magnetic resonance spectroscopy was used to identify spleen metabolites during tumorigenesis. Multi-spectral optoacoustic tomography was used to detect changes in splenic oxygen saturation. Spectrofluorometric measurements determined splenic nitric oxide levels.

Results: Tumorigenesis induced increases in splenic glutathione. Significant splenic glutathione oxidation was observed in E0771 tumor-bearing mice. 4T1 tumorigenesis gave rise to reduced splenic oxygen saturation and the emergence of nitric-oxide-producing cells.

Impact: Tumors induce perturbations in splenic glutathione, reactive species and oxygen saturation which may contribute to poor prognosis and cancer persistence. These findings may provide insight for the development of metabolism-targeted strategies to improve immune surveillance and immunotherapy.

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