Transcriptome dysregulation in hyper-progressive disease samples with immune checkpoint blockade

To the Editor:Tumor immunotherapy has made rapid progress in recent years.However,immune checkpoint blockade(ICB)therapy may cause clinical symptoms of hyper-progressive disease(HPD),especially for patients with alterations or amplifications in driver genes,such as mouse double minute 2(MDM2),epidermal growth factor receptor(EGFR),and fibroblast growth factor 4(FGF4).Recently,Kamada et al[1]investigated the molecular mechanism of HPD to explore whether immune checkpoint inhibition caused HPD in patients in clinical trials.Ki67+effector regulatory T cells(eTregs)in HPD patients were found to be increased after PD-1 monoclonal antibody treatment.Other studies have also found that immune cells in the tumor microenvironment of patients with HPD show obvious changes before and after treatment.[2]Tumor microenvironment changes in HPD imply the potential presence of unknown gene interactions that promote rapid growth of tumor cells after cancer immunotherapy.