Immune checkpoint blockade therapy has achieved remarkable clinical success, but these promising results have been limited to a minority of patients. Thus far, efforts to establish a predictive biomarker or accurately assess early response to treatment have been fruitless. In this issue of Cancer Research, Saida and colleagues utilized advanced molecular imaging modalities to assess changes in the tumor microenvironment that correlate with tumor response to immune checkpoint blockade therapy in vivo This study suggests a combination of imaging biomarkers with potential for delineating clinical response to immunotherapy.See related article by Saida et al., p. 3693.