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Cell Rep Med ; 5(2): 101390, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38340724

RESUMO

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.


Assuntos
Carcinoma de Célula de Merkel , Poliomavírus das Células de Merkel , Oligossacarídeos , Antígeno Sialil Lewis X/análogos & derivados , Neoplasias Cutâneas , Humanos , Carcinoma de Célula de Merkel/tratamento farmacológico , Carcinoma de Célula de Merkel/metabolismo , Carcinoma de Célula de Merkel/patologia , Poliomavírus das Células de Merkel/metabolismo , Receptor de Morte Celular Programada 1/metabolismo , Linfócitos T CD8-Positivos , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/metabolismo , Biomarcadores/metabolismo
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