Targeting metabolism to interrogate immunotherapy resistance in melanoma and predicting therapy efficacy employing HP-MRSI

Motivation: Sensitizing immunotherapy resistant melanoma and interrogating the efficacy of combination treatment at an early stage of treatment resistance can provide physicians with sufficient time to adjust treatment plans and increase survival. Goal(s): Enhancing the sensitivity of immune checkpoint blockade (ICB)-resistant melanoma to immunotherapy by targeting metabolism-related proteins and assessment of treatment efficacy. Approach: Established ICB-resistant B16-F4 melanoma mice were divided into three groups: 1) ICB and monocarboxylate transporter (MCT) inhibitor, 2) ICB, and 3) PBS-treated controls, to assess survival benefits and early efficacy using HP-MRSI. Results: Preliminary HP-MRSI data shows early efficacy of combination therapy of MCT inhibitor and ICB. Impact: The research demonstrates an innovative image-driven pathway to sensitize immunotherapy-resistant melanoma in a preclinical setting. We have shown early efficacy, reduced tumor growth, and improved survival in mice treated with an MCT inhibitor and ICB and interrogated these using HP-MRSI.