Identifying immunotherapy resistance and underlying molecular mechanisms of resistance will help in stratifying immunotherapy treatment effectively. However, identifying immunotherapy resistance and its causative mechanisms are elusive. Here we have developed mouse models of immunotherapy resistance and identified molecular mechanisms indicating immunotherapy resistance employing magnetic resonance. In vitro studies showed adaptations in metabolic pathways of glycolysis, fatty acid and purine synthesis in resistant cell lines. In vivo experiments with 1-13C hyperpolarized pyruvate revealed higher pyruvate to lactate conversion in immunotherapy resistant mice compared to responding ones. Hence, pyruvate to lactate ratio can be a potential biomarker to identify immunotherapy resistance in vivo.