An intratumoral STING agonist-mediated clinical response in PD-L1-refractory MCC via an unexpected mechanism of action

Abstract

Background and aims: Anti-PD-(L)1-refractory MCC portends a grim prognosis with few treatment options. Treatment with agonists of the stimulator of interferon genes (STING) protein is a promising option to promote anti-tumor immunity in PD-(L)1 refractory cancers. Herein, we describe biomarker analyses in a patient with PD-(L)1-refractory, MCPyV+ MCC who had a durable systemic response to a STING agonist administered intratumorally (IT) with concurrent systemic PD-1 blockade. Methods: Serial tumor biopsies and peripheral blood samples taken pre- and post-treatment were analyzed using single cell RNA sequencing (scRNAseq), flow cytometry, T cell receptor sequencing and multiplexed immunohistochemistry (mIHC).