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

Introduction: Head and neck squamous cell carcinoma (HNSCC) is a common and challenging malignancy, showing limited response rates to immune checkpoint inhibitors (ICIs). Accurate blood-based biomarkers for predicting responses to immunotherapy are urgently needed, particularly to aid in stratifying patients in neoadjuvant settings.

Methods: 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.

Results: Six immune markers were significantly elevated in good responders compared to poor responders. These included four percentage-based markers—PD-1ᵈⁱᵐ/CD8⁺T (p = 0.0197), PD-1ʰⁱ/CD8⁺T (p = 0.0011), PD-1⁺/CD8⁺T (p = 0.0034), and CD28⁻PD-1⁺/CD8⁺T (p = 0.0012)—and two mean fluorescence intensity (MFI) values, HLA-DR⁺/CD8⁺T (p = 0.0415) and HLA-DR⁺/CD28⁺PD-1⁻CD8⁺T (p = 0.0425). Among the inflammation-related markers, white blood cell count (WBC, p = 0.0042), neutrophils (Neut, p = 0.0076), and C-reactive protein (CRP, p = 0.0073) were significantly higher in good responders. A combined model of CD28⁻PD-1⁺/CD8⁺ T cells and WBC achieved an area under the curve (AUC) of 0.81 (95% CI: 0.70–0.93), outperforming the Combined Positive Score (CPS) (AUC = 0.59, 95% CI: 0.43–0.76).

Conclusions: This study indicates that peripheral immune and inflammatory markers, particularly the combination of CD28⁻PD-1⁺/CD8⁺ T cells and WBCs, provide a robust predictive model for neoadjuvant immunotherapy response in HNSCC. These findings support the development of personalized treatment strategies and precision immunotherapy, ultimately aiming to enhance clinical outcomes in HNSCC patients.