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

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.