Immunotherapy with immune checkpoint inhibitors (ICIs) changed the treatment management in several solid metastatic tumors with very poor prognosis, in particular in melanoma stage IV since its introduction in 2011. However, it is not yet fully understood why some patients respond to ICIs and others not, and it is also unclear why melanomas are the most sensitive tumors to ICI treatment. Selection criteria for patient stratification are needed and several approaches are under evaluation. These include the PD-L1 expression in the tumor samples, assessment of the tumor mutational burden as well as radiological and molecular imaging techniques, such as positron emission tomography (PET)-CT and PET-MRI with 18F-fluorodeoxyglucose (FDG) or novel radiopharmaceuticals. In the near future, a more holistic approach based on the combination of imaging data and sequencing data and the development of radiogenomic signatures will be needed for a better characterization of immunotherapy response and selection of patients who will benefit from ICI therapy alone or in combination with chemotherapy.
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