Circulating cancer-specific CD8 T cell frequency is associated with response to PD-1 blockade in Merkel cell carcinoma

Thomas Pulliam, Saumya Jani, Lichen Jing, Heeju Ryu, Ana Jojic, Carolyn Shasha, Jiajia Zhang, Rima Kulikauskas, Candice Church, Charlie Garnett-Benson, Ted Gooley, Aude Chapuis, Kelly Paulson, Kellie N. Smith, Drew M. Pardoll, Evan W. Newell, David M. Koelle, Suzanne L. Topalian, Paul Nghiem

Research output: Contribution to journalArticlepeer-review

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 languageEnglish (US)
Article number101412
JournalCell Reports Medicine
Volume5
Issue number2
DOIs
StatePublished - 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

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