Circulating cancer-specific CD8 T cell frequency is associated with response to PD-1 blockade in Merkel cell carcinoma.
Publication Title
Cell Rep Med
Document Type
Article
Publication Date
2-20-2024
Keywords
Humans; Carcinoma, Merkel Cell; CD8-Positive T-Lymphocytes; Programmed Cell Death 1 Receptor; Prospective Studies; Skin Neoplasms; Clinical Trials as Topic; HLA-I; Merkel cell carcinoma; Merkel cell polyomavirus; acquired resistance; anti-PD-1; cancer-specific T cells; nivolumab; primary resistance; skin cancer.; washington; swedish; paul g allen research center; swedish cancer
Abstract
Understanding cancer immunobiology has been hampered by difficulty identifying cancer-specific T cells. Merkel cell polyomavirus (MCPyV) causes most Merkel cell carcinomas (MCCs). All patients with virus-driven MCC express MCPyV oncoproteins, facilitating identification of virus (cancer)-specific T cells. We studied MCPyV-specific T cells from 27 patients with MCC using MCPyV peptide-HLA-I multimers, 26-color flow cytometry, single-cell transcriptomics, and T cell receptor (TCR) sequencing. In a prospective clinical trial, higher circulating MCPyV-specific CD8 T cell frequency before anti-PD-1 treatment was strongly associated with 2-year recurrence-free survival (75% if detectable, 0% if undetectable, p = 0.0018; ClinicalTrial.gov
Area of Special Interest
Cancer
Specialty/Research Institute
Oncology
DOI
10.1016/j.xcrm.2024.101412
