A paradigm shift of PD-L1 immunotherapy based on a tracking-to-triggering immunoediting effect of 2-[18F]FDG

Abstract Efforts have been devoted to select eligible candidates for PD-1/PD-L1 immune checkpoint blocker (ICB) immunotherapy based on radiopharmaceuticals. Here, we have observed a tracking-to-triggering (referred to as “T2T”) immunoediting effect of the employed radionuclides. In particular, we found the usefulness of 2-[18F]FDG in cancer ICB therapy. Given that the PD-L1 expression is upregulated after the administration of various radiotracers, the predictive result from PET/SPECT imaging should be treated with caution. Viewed positively, radiotracers are potential immunomodulators to create an immune-favorable microenvironment for tumor immunotherapy. Improving αPD-L1 mAb utilization and significant tumor growth delay are observed when the personalized therapeutic alliance of radiotracer stimulation and ICB are employed. This new paradigm has the potential to expand the traditional tumor theranostic model and implement precision cancer immunotherapy.