Abstract Immune checkpoint inhibitors (ICIs) have improved outcomes in recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC), yet reliable biomarkers predicting response to 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 using 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.
Kumai et al. (Wed,) studied this question.