451 Blockade of tumor cell-intrinsic PD-1 inhibits Merkel cell carcinoma growth

Merkel Cell Carcinoma (MCC) is a rare, but highly aggressive cancer of the skin. In MCC patients, inhibitors targeting programmed cell death-1 (PD-1) immune checkpoint pathway have yielded remarkable antitumor activity by stimulating cancer-specific T-cell immunity. Here, we identify previously unknown role for PD-1 as growth-promoting receptor intrinsic to cells. four established human lines, MKL-1, MKL-2, MS-1, and WaGa, RT-PCR amplification sequencing revealed expression full (PDCD1) mRNA coding sequence. Immunoblot FACS analyses demonstrated protein expression. Immunofluorescence staining also CK20+CD45- cells in clinical tumor biospecimens. Binding MCC-PD-1 its ligands, PD-L1 or PD-L2, induced protumorigenic mTOR signaling mitochondrial reactive oxygen species (mROS) generation, both which were inhibited clinically approved blocking antibody, nivolumab. Consistently, blockade suppressed vitro proliferation vivo xenograft growth mice lacking adaptive Our results MCC-intrinsic novel growth-accelerating mechanism therapeutic target, might contribute inhibitor efficacy patients.