Department of Oral and Maxillofacial Diseases, Clinicum, University of Helsinki, Helsinki, Finland.
Department of Pathology, São Leopoldo Mandic Research Centre, Campinas, Brazil.
J Oral Pathol Med. 2018 Sep;47(8):773-780. doi: 10.1111/jop.12737. Epub 2018 Jun 20.
Oral mucosal dysplasia is a histologic feature of potentially malignant disorders that is associated with the risk of transformation to carcinoma. Dysplastic cells use many strategies during their transformation to cancer, including escape from the immune mediated destruction. We hypothesized that adaptive immunity is inhibited by activation of distinct immune checkpoint molecules, such as indoleamine 2,3-dioxygenase 1 (IDO1) and programmed death-ligand 1 (PD-L1).
We collected 63 oral dysplasia samples from 47 patients. Nine biopsies from alveolar mucosa were taken during wisdom teeth extractions were used as healthy controls. Tissue samples were stained and scored for IDO1 and PD-L1. Additionally, dysplasia grades and inflammatory cell infiltration were evaluated. Eight patients were followed up to 36 months to evaluate dysplasia progression, inflammation, and immune checkpoint molecules expression.
Dysplastic epithelium had significantly lower IDO1 expression than that of healthy controls. PD-L1 positive cells in the lamina propria were mainly in dysplastic samples and seldom in healthy controls. Dysplasia grade was associated negatively with epithelium IDO1 and positively with IDO1 and PD-L1 expression in the lamina propria. There was a positive association between dysplasia grade and level of inflammatory cell infiltration. During follow-up, dysplasia grade, inflammatory cell infiltration, and the immune checkpoint expression fluctuated over time.
Immune checkpoint molecules IDO1 and PD-L1 are modulated during oral epithelial dysplastic changes, and their expression is associated with inflammatory cell infiltration in the lamina propria. As immune checkpoint molecules expression fluctuates over time, these molecules are not useful as biomarkers for oral mucosal dysplasia progression.
口腔黏膜异型增生是一种潜在恶性疾病的组织学特征，与癌变的风险相关。异型增生细胞在向癌症转化的过程中会使用多种策略，包括逃避免疫介导的破坏。我们假设适应性免疫受到独特免疫检查点分子的激活抑制，如吲哚胺 2,3-双加氧酶 1（IDO1）和程序性死亡配体 1（PD-L1）。
我们从 47 名患者中收集了 63 例口腔异型增生样本。在拔除智齿时从 9 例牙槽黏膜活检获得正常对照组织。对组织样本进行 IDO1 和 PD-L1 染色和评分。此外，评估异型增生分级和炎症细胞浸润。对 8 例患者进行了 36 个月的随访，以评估异型增生进展、炎症和免疫检查点分子表达。
异型增生上皮的 IDO1 表达明显低于正常对照组。固有层中 PD-L1 阳性细胞主要存在于异型增生样本中，而在正常对照组中很少见。异型增生分级与上皮 IDO1 呈负相关，与固有层中 IDO1 和 PD-L1 表达呈正相关。异型增生分级与炎症细胞浸润水平呈正相关。在随访过程中，异型增生分级、炎症细胞浸润和免疫检查点表达随时间波动。
免疫检查点分子 IDO1 和 PD-L1 在口腔上皮异型增生变化过程中被调节，其表达与固有层中炎症细胞浸润相关。由于免疫检查点分子的表达随时间波动，因此它们不能作为口腔黏膜异型增生进展的生物标志物。
