Peripheral immune and inflammatory markers as predictors of neoadjuvant immunotherapy response in head and neck squamous cell carcinoma

Head and neck squamous cell carcinoma (HNSCC) is a common and challenging malignancy, with limited response rates to immune checkpoint inhibitors (ICIs). Accurate blood-based biomarkers are needed to predict immunotherapy responses, aiding patient stratification in neoadjuvant settings. Baseline peripheral blood samples were collected from 52 newly diagnosed HNSCC patients undergoing neoadjuvant ICI therapy. Immune cell phenotypes were assessed using flow cytometry across three staining panels: Panel A (CD3, CD4, CD8, PD-1, CD28, HLA-DR), Panel B (CD3, CD4, CD8, KLRG-1, CD57), and Panel C (CD3, CD4, CD8, CD45RA, CCR7, CD28, CD38). Retrospective analysis included routine blood counts, biochemical markers, and cytokine levels. The predictive accuracy of individual and combined biomarkers was evaluated using receiver operating characteristic (ROC) curve analysis. Six immune markers were elevated in non-responder group (non-R group), including PD-1^dim/CD8⁺ T, PD-1ʰⁱ/CD8⁺ T, PD-1⁺/CD8⁺ T, and CD28^–PD-1⁺/CD8⁺ T as percentage markers, and HLA-DR⁺/CD8⁺ T and HLA-DR⁺/CD28⁺PD-1^–CD8⁺ T as mean fluorescence intensity (MFI) markers. Inflammation markers, including WBC, neutrophils (Neut), and CRP, also correlated with response. A combined model of CD28^–PD-1⁺/CD8⁺ T cells and WBC achieved an area under the curve (AUC) of 0.82 (95% CI: 0.69–0.94), outperforming the Combined Positive Score (CPS; AUC = 0.59, 95% CI: 0.43–0.76). These findings suggest that peripheral immune and inflammatory markers, particularly CD28^–PD-1⁺/CD8⁺ T cells and WBC, can predict ICI response, supporting personalized immunotherapy in HNSCC.