Transcriptional downregulation of MHC class I and melanoma de- differentiation in resistance to PD-1 inhibition.

ABSTRACT: Transcriptomic signatures designed to predict melanoma patient responses to PD-1 blockade have been reported but rarely validated. We now show that intra-patient heterogeneity of tumor responses to PD-1 inhibition limit the predictive performance of these signatures. We reasoned that resistance mechanisms will reflect the tumor microenvironment, and thus we examined PD-1 inhibitor resistance relative to T-cell activity in 94 melanoma tumors collected at baseline and at time of PD-1 inhibitor progression. Tumors were analyzed using RNA sequencing and flow cytometry, and validated functionally. These analyses confirm that major histocompatibility complex (MHC) class I downregulation is a hallmark of resistance to PD-1 inhibitors and is associated with the MITF^low/AXL^high

SUBMITTER: Lee JH 

PROVIDER: S-EPMC7171183 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature