Merkel cell polyomavirus-specific and CD39 + CLA + CD8 T cells as blood-based predictive biomarkers for PD-1 blockade in Merkel cell carcinoma.

Merkel cell carcinoma is a skin cancer often driven by Merkel cell polyomavirus (MCPyV) with high rates of response to anti-PD-1 therapy despite low mutational burden. MCPyV-specific CD8 T cells are implicated in anti-PD-1-associated immune responses and provide a means to directly study tumor-specific T cell responses to treatment. Using mass cytometry and combinatorial tetramer staining, we find that baseline frequencies of blood MCPyV-specific cells correlated with response and survival. Frequencies of these cells decrease markedly during response to therapy. Phenotypes of MCPyV-specific CD8 T cells have distinct expression patterns of CD39, cutaneous lymphocyte-associated antigen (CLA), and CD103. Correspondingly, overall bulk CD39 ⁺ CLA ⁺ CD8 T cell frequencies in blood correlate with MCPyV-specific cell frequencies and similarly predicted favorable clinical outcomes. Conversely, frequencies of CD39 ⁺ CD103 ⁺ CD8 T cells are associated with tumor burden and worse outcomes. These cell subsets can be useful as biomarkers and to isolate blood-derived tumor-specific T cells.
Competing Interests: Declaration of interests E.W.N. is a co-founder, advisor, and shareholder for ImmunoScape Pte. Ltd., a scientific advisory board member and shareholder for Neogene Therapeutics, and a scientific advisory board member for Nanostring Biotechnologies and Trojan Biotechnologies. D.M.K. and P.N. are co-inventors on an institutionally owned patent concerning MCPyV-specific TCRs.
(Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)