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-1dim/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.头颈部鳞状细胞癌（Head and neck squamous cell carcinoma, HNSCC）是一类常见且极具治疗挑战的恶性肿瘤，对免疫检查点抑制剂（immune checkpoint inhibitors, ICIs）的应答率有限，亟需精准的血液生物标志物以预测免疫治疗应答，辅助新辅助治疗场景下的患者分层。本研究收集了52例初诊且接受新辅助ICI治疗的HNSCC患者的基线外周血样本。采用三种染色组合（staining panels）通过流式细胞术（flow cytometry）分析免疫细胞表型：组合A包含CD3、CD4、CD8、PD-1、CD28、HLA-DR；组合B包含CD3、CD4、CD8、KLRG-1、CD57；组合C包含CD3、CD4、CD8、CD45RA、CCR7、CD28、CD38。回顾性分析涵盖血常规、生化标志物及细胞因子水平。采用受试者工作特征曲线（receiver operating characteristic curve, ROC）分析评估单个及联合生物标志物的预测效能。结果显示，无应答组（non-R组）存在6种免疫标志物表达升高：包括以百分比计量的PD-1dim/CD8+ T细胞、PD-1hi/CD8+ T细胞、PD-1+/CD8+ T细胞及CD28–PD-1+/CD8+ T细胞，以及以平均荧光强度（mean fluorescence intensity, MFI）计量的HLA-DR+/CD8+ T细胞和HLA-DR+/CD28+PD-1–CD8+ T细胞。包括白细胞（WBC）、中性粒细胞（Neut）及C反应蛋白（CRP）在内的炎症标志物也与治疗应答存在相关性。联合CD28–PD-1+/CD8+ T细胞与WBC的预测模型的曲线下面积（area under the curve, AUC）达0.82（95%置信区间（confidence interval, CI）：0.69–0.94），其性能优于综合阳性评分（Combined Positive Score, CPS）的AUC值0.59（95%置信区间：0.43–0.76）。本研究结果表明，外周血免疫及炎症标志物，尤其是CD28–PD-1+/CD8+ T细胞与WBC，可有效预测ICI治疗应答，可为HNSCC患者的个性化免疫治疗提供支持。