Arginine metabolism is involved in many cell functions and plays an important role among others in the regulation of immune cell reactivity and carcinogenesis. For instance, while Arginine is essential for T cell activity, TAMs and MDSCs – through the expression and activity of Arginase – favor its degradation thereby participating in immunosuppression.
Novel therapeutic options in immuno-oncology consist in manipulating such a metabolic pathway to relieve the function of immunosuppressive macrophages. For instance, Arginase 1 can be targeted directly through the use of Arginase inhibitors (eg. INCB-001158) or indirectly through the modulation of specific signaling pathways (eg. PI3K). Finally, whatever the mechanism of action of drug candidates, Arginine remains a suitable surrogate biomarker of Arginase activity and its quantification can now be approached by ELISA!