Objective: To investigate the relationship between the expression of CD103+CD8+T cells in locally advanced oral squamous cell carcinoma (LA-OSCC), and the response to neoadjuvant chemoimmunotherapy (NACI). Methods: Thirty LA-OSCC patients from the Department of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, who underwent NACI from June 2020 to December 2022 were analyzed, including 16 responders and 14 non-responders. Using multiple immunofluorescence technique to stain sections of patients to verify the correlation between the expression of CD103+CD8+T cells and the efficacy of NACI. CD103+CD8+T cell density was counted using Inform and HALO software. The Spearman correlation coefficient in rank correlation is used to describe the correlation between CD103+CD8+T cell and neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), platelet-lymphocyte ratio (PLR), systemic immune inflammation index (SII) It's effectiveness as a predictive marker to NACI was analyzed by receiver operator characteristic (ROC) curve analysis and decision curve analysis (DCA). Two-tailed t-test or Mann-Whitney U-test was used to compare data between two groups, and one-way ANOVA was used to compare data between multiple groups. SPSS 22.0 and GraphPad prism 9.0 software were used for statistical analysis and plotting of relevant statistical graphs such as histograms. P<0.05 was considered a statistically significant difference. Results: The density of CD103+CD8+T cells has expanded in advanced OSCC patients who are responsive to NACI. The CD103+CD8+T cell densities in the responsive and nonresponsive groups were 118.30(41.92, 197.80) pcs/mm2 and 21.63(4.91, 71.92) pcs/mm2 respectively, with statistically significant differences(U=52.00, P=0.012). CD103+CD8+T cell abundance was negatively correlated with NLR, dNLR, PLR, and SII (P<0.05). ROC curve analysis showed that the AUC for predicting efficacy of NLR, dNLR, PLR, and SII were 0.781 (P=0.009, 95%CI: 0.5715-0.9910), 0.671 (P=0.105, 95%CI: 0.467-0.881), 0.679 (P=0.020 95%CI: 0.549-0.951), 0.750 (P=0.096, 95%CI: 0.461-0.896), respectively. The AUC for CD103+CD8+T cells alone was 0.861 (P=0.013, 95%CI: 0.585-0.950), and the AUC of combining CD103+CD8+T cells with NLR was 0.896 (P=0.025, 95%CI: 0.454-0.938). Conclusions: The density of CD103+CD8+T cells is expanded in advanced OSCC patients who are responsive to NACI. CD103+CD8+T cells positively predict favorable responses as a strong indicator to NACI in advanced OSCC patients. Co-interpretation of CD103+CD8+T cells and NLR value enhances the predictive accuracy of NACI in advanced OSCC patients.
目的： 探讨CD103+CD8+T 细胞在经新辅助化免联合治疗（NACI）的局部晚期口腔鳞状细胞癌（LA-OSCC）患者中的表达水平和临床意义。 方法： 分析2020年6月至2022年12月于中山大学孙逸仙纪念医院口腔颌面外科接受NACI的LA-OSCC患者30例，其中响应者16例（响应组），非响应者14例（非响应组）。利用多重免疫荧光技术对患者活检肿瘤组织切片染色，明确CD103+CD8+T细胞密度与NACI疗效的相关性。采用Inform、HALO软件统计肿瘤组织内CD103+CD8+T细胞的表达丰度，通过皮尔逊相关系数分析CD103+CD8+T细胞与4种肿瘤炎症标志物的相关性，包括中性粒细胞与淋巴细胞比值（NLR）、嗜中性白细胞与淋巴细胞比值（dNLR）、血小板与淋巴细胞比值（PLR）及系统免疫炎症指数（SII）。应用多因素二元Logistic回归分析评估代表PD-L1表达水平的联合阳性评分（CPS）、CD103+CD8+T细胞丰度以及肿瘤炎症标志物NLR、dNLR、PLR、SII对患者NACI疗效的影响。采用受试者操作特征（ROC）曲线分析和决策曲线分析这些指标作为NACI疗效预测靶点的有效性。使用SPSS 22.0和GraphPad Prism 9.0 软件进行统计分析及绘图。以双侧P<0.05为差异有统计学意义。 结果： NACI响应组的CD103+CD8+T细胞密度［118.30（41.92，197.80）个/mm2］显著高于非响应组［21.63（4.91，71.92）个/mm2］（U=52.00，P=0.012）。ROC曲线分析显示，CD103+CD8+T细胞的预测效能［0.861（95%CI：0.585~0.950，P=0.013）］显著大于CPS的预测效能［0.734（95%CI：0.552~0.917，P=0.029）］（P=0.037）。CD103+CD8+T 细胞丰度与NLR、dNLR、PLR、SII均呈负相关（P<0.05）。NLR、dNLR、PLR、SII预测疗效的曲线下面积（AUC）分别为0.781、0.674、0.679及0.750。单独使用CD103+CD8+T 细胞预测疗效的AUC为0.861，CD103+CD8+T 细胞与NLR联合预测疗效的AUC为0.896（P=0.025，95%CI：0.454~0.938）。 结论： 本研究发现LA-OSCC中，CD103+CD8+T细胞表达水平与患者NACI治疗响应程度呈正相关，而联合NLR可以对NACI疗效具有一定的预测作用。.