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Peripheral immune and inflammatory markers as predictors of neoadjuvant immunotherapy response in head and neck squamous cell carcinoma
1 , 1 , 2 , * 1
1  Department of Clinical Laboratory, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
2  Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Academic Editor: Luca Bertolaccini

Published: 17 March 2025 by MDPI in The 1st International Online Conference on Clinical Reports session Cancer
Abstract:

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.

Keywords: Head and neck squamous cell carcinoma (HNSCC); immune checkpoint inhibitors (ICIs); peripheral blood; neoadjuvant immunotherapy

 
 
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