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: NCT02488759). Intratumorally, such T cells were typically present, but their frequency did not significantly associate with response. Circulating MCPyV-specific CD8 T cells had increased stem/memory and decreased exhaustion signatures relative to their intratumoral counterparts. These results suggest that cancer-specific CD8 T cells in the blood may play a role in anti-PD-1 responses. Thus, strategies that augment their number or mobilize them into tumors could improve outcomes.
Original language | English (US) |
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Article number | 101412 |
Journal | Cell Reports Medicine |
Volume | 5 |
Issue number | 2 |
DOIs | |
State | Published - Feb 20 2024 |
Keywords
- HLA-I
- Merkel cell carcinoma
- Merkel cell polyomavirus
- acquired resistance
- anti-PD-1
- cancer-specific T cells
- nivolumab
- primary resistance
- skin cancer
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology