Circulating cancer-specific CD8 T cell frequency is associated with response to PD-1 blockade in Merkel cell carcinoma.
Document Type
Article
Publication Date
2-20-2024
Publication Title
Cell Rep Med
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: 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.
Clinical Institute
Cancer
Department
Oncology
Recommended Citation
Pulliam, Thomas; Jani, Saumya; Jing, Lichen; Ryu, Heeju; Jojic, Ana; Shasha, Carolyn; Zhang, Jiajia; Kulikauskas, Rima; Church, Candice; Garnett-Benson, Charlie; Gooley, Ted; Chapuis, Aude; Paulson, Kelly G; Smith, Kellie N; Pardoll, Drew M; Newell, Evan W; Koelle, David M; Topalian, Suzanne L; and Nghiem, Paul, "Circulating cancer-specific CD8 T cell frequency is associated with response to PD-1 blockade in Merkel cell carcinoma." (2024). Articles, Abstracts, and Reports. 8521.
https://digitalcommons.providence.org/publications/8521