Metabolic and Functional Imaging Biomarkers of Response to Immunotherapy in Melanoma

Motivation: Studying immunotherapy effects at the subcellular level in melanoma may reveal critical biomarkers of response and improve therapeutic strategies. Goal(s): We aim to study the impact of anti-PD-1 immunotherapy on metabolite levels, bioenergetics, pH, diffusivity, and T2 relaxation times in immunogenic melanoma models. Approach: We used in vivo MRI and MRS to assess the impact of anti-PD-1 immunotherapy on the immunogenic melanoma model YUMMER1.7. Results: Early-phase changes in lactate, alanine, pH, bioenergetics, ADC, and T2 relaxation time occurred during anti-PD-1 immunotherapy. Preliminary in vitro studies with two metabolic modulators further characterized the metabolic phenotypes of isolated YUMMER1.7 melanoma cells. Impact: This study emphasizes the potential of early subcellular changes (metabolism, pH, bioenergetics, diffusion, T2 relaxation) as predictive biomarkers of melanoma immunotherapy response. Preliminary findings with metabolic modulators indicate possible strategies for enhancing treatment outcomes through metabolic modulation.