Cancer-specific CD8 T cell frequency at baseline in blood correlates with response to PD-1 blockade in Merkel cell carcinoma
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ABSTRACT: Understanding immunotherapy response and resistance is challenging due to difficulty identifying cancer-specific CD8 T cells. Merkel cell carcinoma (MCC) is typically driven by Merkel cell polyomavirus (MCPyV), facilitating identification of cancer-specific T cells across patients. We characterized cancer-specific T cells in 35 MCC patients, including from a neoadjuvant anti-PD-1 trial. Higher MCPyV-specific CD8 T-cell frequency in pre-treatment blood (but not tumors) correlated with response (p=0.0056). Single cell RNAseq revealed MCPyV-specific CD8 T cells in blood with increased stem/memory signatures and decreased exhaustion signatures relative to their intratumoral counterparts. Number of circulating cancer-specific T cells is likely most linked to primary response to immunotherapy as longitudinal samples documented emergence of additional resistance mechanisms, amidst abundant circulating cancer-specific CD8 T cells. These results suggest that blood acts as an important reservoir of cancer-specific CD8 T cells and suggests adoptive cell therapies may be particularly effective in patients without such cells.
ORGANISM(S): Homo sapiens
PROVIDER: GSE227054 | GEO | 2023/04/01
REPOSITORIES: GEO
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