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

ESDR451 - Blockade of tumor cell-intrinsic PD-1 inhibits Merkel cell carcinoma growth

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.