Abstract：
BACKGROUND: Despite recent advances in the use of immune checkpoint blockade (ICB) across various cancer types, its efficacy in odontogenic carcinomas remains unexplored. This study aims to investigate PD-L1 expression and the tumor immune microenvironment (TIME) in odontogenic carcinomas to determine the therapeutic potential of ICB and the significance of immune markers.
METHODS: The expressions of PD-L1 and T cell markers (CD3, CD8, and FOXP3) were visualized by immunohistochemistry in 21 tissue samples of odontogenic carcinomas. Tumoral PD-L1 expression and the density and spatial distribution of T cell subsets were evaluated, from which TIME was determined. The associations of the variables with clinicopathological and prognostic factors were statistically analyzed.
RESULTS: PD-L1 was positively expressed in 52.4% (11/21) of the cases studied. Among tumor types, ameloblastic carcinoma showed significantly higher PD-L1 expression (p = 0.016). TIME based on the intratumoral and stromal T cell distribution was immune-inflamed in 61.9% (13/21) and immune-excluded in 38.1% (8/21), with no immune-desert cases. PD-L1 expression was associated with the densities of all intratumoral T cell subsets (p = 0.03 for CD3, p = 0.03 for CD8, and p = 0.008 for FOXP3) but not with those of stromal T cells. High PD-L1 expression was associated with larger tumor size (p = 0.021), while the intratumoral CD8/CD3 ratio was inversely correlated with tumor size (p = 0.048).
CONCLUSIONS: These findings indicate the involvement of adaptive immune resistance in a subset of odontogenic carcinomas and support the therapeutic potential of ICB in patients with these rare malignancies.
METHODS: The expressions of PD-L1 and T cell markers (CD3, CD8, and FOXP3) were visualized by immunohistochemistry in 21 tissue samples of odontogenic carcinomas. Tumoral PD-L1 expression and the density and spatial distribution of T cell subsets were evaluated, from which TIME was determined. The associations of the variables with clinicopathological and prognostic factors were statistically analyzed.
RESULTS: PD-L1 was positively expressed in 52.4% (11/21) of the cases studied. Among tumor types, ameloblastic carcinoma showed significantly higher PD-L1 expression (p = 0.016). TIME based on the intratumoral and stromal T cell distribution was immune-inflamed in 61.9% (13/21) and immune-excluded in 38.1% (8/21), with no immune-desert cases. PD-L1 expression was associated with the densities of all intratumoral T cell subsets (p = 0.03 for CD3, p = 0.03 for CD8, and p = 0.008 for FOXP3) but not with those of stromal T cells. High PD-L1 expression was associated with larger tumor size (p = 0.021), while the intratumoral CD8/CD3 ratio was inversely correlated with tumor size (p = 0.048).
CONCLUSIONS: These findings indicate the involvement of adaptive immune resistance in a subset of odontogenic carcinomas and support the therapeutic potential of ICB in patients with these rare malignancies.
摘要：
背景：尽管在各种癌症类型中使用免疫检查点阻断（ICB）的最新进展，其在牙源性癌中的疗效尚待探索。本研究旨在研究牙源性癌中PD-L1的表达和肿瘤免疫微环境（TIME），以确定ICB的治疗潜力和免疫标志物的意义。
方法：通过免疫组织化学观察21例牙源性癌组织样本中PD-L1和T细胞标志物（CD3，CD8和FOXP3）的表达。评估肿瘤PD-L1的表达以及T细胞亚群的密度和空间分布。时间是确定的。统计分析各变量与临床病理和预后因素的关系。
结果：PD-L1在52.4%（11/21）的病例中呈阳性表达。在肿瘤类型中，成釉细胞癌的PD-L1表达明显增高(p=0.016)。基于肿瘤内和基质T细胞分布的时间为61.9％（13/21）的免疫炎症和38.1％（8/21）的免疫排除，没有免疫沙漠病例。PD-L1表达与所有肿瘤内T细胞亚群的密度相关（CD3的p=0.03，CD8的p=0.03，FOXP3的p=0.008），但与基质T细胞的密度无关。PD-L1高表达与较大的肿瘤大小相关（p=0.021），而肿瘤内CD8/CD3比值与肿瘤大小呈负相关（p=0.048）。
结论：这些研究结果表明适应性免疫抵抗参与了牙源性癌的一部分，并支持ICB在这些罕见恶性肿瘤患者中的治疗潜力。
方法：通过免疫组织化学观察21例牙源性癌组织样本中PD-L1和T细胞标志物（CD3，CD8和FOXP3）的表达。评估肿瘤PD-L1的表达以及T细胞亚群的密度和空间分布。时间是确定的。统计分析各变量与临床病理和预后因素的关系。
结果：PD-L1在52.4%（11/21）的病例中呈阳性表达。在肿瘤类型中，成釉细胞癌的PD-L1表达明显增高(p=0.016)。基于肿瘤内和基质T细胞分布的时间为61.9％（13/21）的免疫炎症和38.1％（8/21）的免疫排除，没有免疫沙漠病例。PD-L1表达与所有肿瘤内T细胞亚群的密度相关（CD3的p=0.03，CD8的p=0.03，FOXP3的p=0.008），但与基质T细胞的密度无关。PD-L1高表达与较大的肿瘤大小相关（p=0.021），而肿瘤内CD8/CD3比值与肿瘤大小呈负相关（p=0.048）。
结论：这些研究结果表明适应性免疫抵抗参与了牙源性癌的一部分，并支持ICB在这些罕见恶性肿瘤患者中的治疗潜力。
