Floor Brushes Summary: The immune-genetic changes that occur in cancer patients experiencing hyperprogressive disease (HPD) during combined immunotherapy are unclear.In this study, HPD patients with pre- and post-HPD samples and non-HPD patients with solid tumors were molecularly characterized by genetic and tumor immune microenvironment (TiME) analyses of paired samples by whole-exome sequencing, RNA sequencing, and multiplex immunofluorescence.The genetic analysis of paired samples showed that almost all the tumor driver gene mutations were preserved between pre- and post-HPD tumors.
HPD patients had higher frequencies of mutations in TP53 and CNN2, and a significantly higher mutant-allele tumor heterogeneity than non-HPD patients.Tumor IL-6 mRNA was upregulated in post-HPD samples vs.pre-HPD, Skin Lotion accompanied by a potential immune suppressive TiME with an elevated M2/M1 ratio.
Salvage treatment with irinotecan plus bevacizumab was effective in one HPD patient, who experienced prolonged survival.These genetic features and TiME characteristics might help identify the features of HPD after immunotherapy.