Molecular imaging to enlighten cancer immunotherapies and underlying involved processes

•Molecular imaging enables visualization of important components involved in immunotherapy.•Radiopharmaceuticals can target tumor cells, immune cells and extracellular matrix components.•Molecular imaging strategies might provide insight into mechanisms responsible for immunotherapy treatment effects.•Molecular imaging might contribute to patient selection for immunotherapy. Cancer immunotherapy has led to impressive antitumor effects. However, not all patients respond to immunotherapy, serious toxicity can occur and combination therapy may be warranted. Strategies for rational early treatment choices are urgently required. In the absence of ideal accompanying biomarkers it remains challenging to capture the dynamic, heterogeneous and complex tumor behavior. Tumor immune response involves next to tumor cells, numerous other cells and molecules in the tumor microenvironment. We review research to identify potential novel imaging biomarkers by non-invasive whole body molecular imaging with positron emission tomography and single-photon emission computed tomography for cancer immunotherapy. Firstly, imaging with radiolabeled immune checkpoint targeting molecules. Secondly, imaging of immune cells with ex vivo or in vivo radiolabeled tracers and thirdly, imaging extracellular matrix components, including adhesion molecules, growth factors and cytokines. These molecular imaging strategies – used alone, in combination or serially – could potentially contribute to patient selection upfront or early during immunotherapy.