T Cell Receptor Repertoire in Cell-Free DNA as a Proxy for Tumor Infiltrates in Patients Treated with Pembrolizumab

Strategic Insights -

Researchers at the University Health Network in Toronto, Canada, have conducted a study to investigate the diversity and specificity of T cell receptor (TCR) sequences in patients with solid tumors treated with pembrolizumab. The study analyzed TCR sequences from tumor, peripheral blood mononuclear cell (PBMC), and cell-free DNA (cfDNA) samples from 81 patients. The analysis revealed that head and neck carcinomas have significantly lower PBMC diversity and shorter persistence of pembrolizumab-induced diversification compared to other cancers. Furthermore, the study found that tumor-derived clonotypes form non-microbial specificity signatures that are shared across patients and cancer types.

Key Takeaways:

  • The study analyzed TCR sequences from 58 tumor, 306 PBMC, and 73 cfDNA samples from 81 patients with solid tumors treated with pembrolizumab.
  • Head and neck carcinomas had significantly lower PBMC diversity and shorter persistence of pembrolizumab-induced diversification compared to other cancers.
  • Tumor-derived clonotypes formed non-microbial specificity signatures that were shared across patients and cancer types.
  • cfDNA TCR repertoires were two orders of magnitude lower than PBMCs.
  • TCRs shared between tumors and cfDNAs persisted in PBMCs beyond 50 weeks of treatment, suggesting that cfDNA captures clonotypes contributing to anti-tumor immune surveillance.
  • The study identified features associated with the clinical benefit of patients with cancer on immune checkpoint blockade therapy.

Statistics:

  • 81 patients with solid tumors were treated with pembrolizumab in the study.
  • 58 tumor, 306 PBMC, and 73 cfDNA samples were analyzed in the study.
  • TCR sequences were analyzed from studied samples.
  • Head and neck carcinomas had PBMC diversity that was 2.5 times lower than other cancers.
  • cfDNA TCR repertoires were two orders of magnitude lower than PBMCs.

Sources:

  • NewsRx. Researchers at University Health Network Have Reported New Data on Monoclonal Antibodies (T cell receptor repertoire in cell-free DNA as a proxy for tumor infiltrates in patients treated with pembrolizumab). Cancer Weekly. September 16, 2025; p 6229.
  • "T cell receptor repertoire in cell-free DNA as a proxy for tumor infiltrates in patients treated with pembrolizumab". Cell Reports, 2025;44(9):116190.