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Fred Hutchinson Cancer Center

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Cell Rep. Med., Jan 30 2024, S2666-3791(23)00619-5 | https://doi.org/10.1016/j.xcrm.2023.101390 Merkel cell polyomavirus-specific and CD39+CLA+ CD8 T cells as blood-based predictive biomarkers for PD-1 blockade in Merkel cell carcinoma

HeejuRyu,¹ TimothyM.Bi,¹ ThomasH.Pulliam,² KorokSarkar,¹ CandiceD.Church,² NanditaKumar,^1,3 KoshlanMayer-Blackwell,¹ SaumyaJani,^2,3 NirashaRamchurren,⁴ UllaK.Hansen,⁵ SineR.Hadrup,⁵ StevenP.Fling,⁴ DavidM.Koelle,^1,3,6,7,8 PaulNghiem,² and EvanW.Newell ^1,3,9,*

¹Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA
²Department of Medicine, Division of Dermatology, University of Washington, Seattle, WA, USA
³Department of Lab Medicine and Pathology, University of Washington, Seattle, WA, USA
⁴Cancer Immunotherapy Trails Network, Fred Hutchinson Cancer Center, Seattle, WA, USA
⁵Department of Health Technology, Technical University of Denmark, Kongens Lyngby, Denmark
⁶DepartmentofMedicine,DivisionofAllergyandInfectiousDiseases,UniversityofWashington,Seattle,WA,USA
⁷Department of Global Health, University of Washington, Seattle, WA, USA
⁸Benaroya Research Institute, Seattle, WA, USA
⁹Lead contact

^*Corresponding author: correspondence to EvanW.Newell

Abstract

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.

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형식Research article
게재일2024년 01월 (BRIC 등록일 2024-02-15)
연구진국외 연구진
분야 의약학 > 면역의학

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