Peptide-Reactive T-cell Response as a Novel Biomarker in Patients with Head and Neck Cancer Treated with Anti-PD-1...

Immune checkpoint inhibitors have improved outcomes in recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC), yet reliable biomarkers predicting response to programmed death 1 (PD-1) blockade remain limited. We retrospectively analyzed 40 patients with R/M HNSCC treated with nivolumab or pembrolizumab monotherapy, evaluating clinical data, laboratory parameters, PD-L1 expression, tumor-infiltrating T cells, and peripheral immune features. Peripheral blood mononuclear cells obtained before treatment were assessed by flow cytometry for exhaustion markers and short-term tumor antigen-derived peptide stimulation with IFN-γ ELISA. The objective response rate was 18%, with median overall survival of 13 months and progression-free survival of 3 months. PD-L1 expression and densities of CD4+, CD8+, and FoxP3+ T cells were not associated with response. In contrast, responders more frequently developed immune-related adverse events and had preserved cervical lymph nodes. Favorable responses were associated with higher baseline lymphocyte and lower neutrophil percentages, as well as lower frequencies of CD38+ CD8+ T cells. Notably, c-Met-derived peptide stimulation induced significantly higher IFN-γ production in responders, indicating the presence of circulating tumor antigen-reactive T cells. These findings suggest that tumor antigen-reactive T cells, together with a favorable systemic immune profile, are associated with clinical benefit from PD-1 blockade and that peripheral blood-based peptide-reactive T-cell assays may provide a practical approach for biomarker development in R/M HNSCC.

c-Met-specific circulating tumor antigen-reactive T cells predict response to PD-1 blockade in R/M HNSCC. Favorable systemic immunity further supports outcomes. Peripheral blood-based assays offer a practical, noninvasive biomarker to identify patients most likely to benefit from immunotherapy.