Immunogenomic Landscape Contributes to Hyperprogressive Disease after Anti-PD-1 Immunotherapy for Cancer.

ABSTRACT: Although PD-1-blocking immunotherapies demonstrate significant therapeutic promise, a subset of the patients could develop hyperprogressive disease (HPD) with accelerated tumor growth after anti-PD1 immunotherapy. To elucidate the underlying mechanisms, we compared the mutational and transcriptional landscapes between the pre- and post-therapy tumors of two patients developing HPD after anti-PD-1 immunotherapy. In post-therapy HPD tumors, somatic mutations were found in known cancer genes, including tumor suppressor genes such as TSC2 and VHL, along with transcriptional upregulation of oncogenic pathways, including IGF-1, ERK/MAPK, PI3K/AKT, and TGF-β. We found that post-therapy HPD tumors were less immunogenic than pre-therapy tumors, concurrent with an increased presence of ILC3 cells, a

SUBMITTER: Xiong D 

PROVIDER: S-EPMC6234258 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature