Fernandes Darcy, Barbeiro Camila de Oliveira, Palaçon Mariana Paravani, Biancardi Mariel Ruivo, Ferrisse Túlio Morandin, Silveira Heitor Albergoni, Castilho Rogerio Moraes, de Almeida Luciana Yamamoto, Leon Jorge Esquiche, Bufalino Andreia
Oral Medicine, Department of Diagnosis and Surgery, São Paulo State University (Unesp), School of Dentistry, Araraquara, São Paulo, Brazil.
Laboratory of Epithelial Biology, Department of Periodontics and Oral Medicine, University of Michigan, School of Dentistry, Ann Arbor, Michigan, USA.
Immunology. 2023 Jan;168(1):96-109. doi: 10.1111/imm.13565. Epub 2022 Sep 3.
Oral leukoplakia (OL) and proliferative verrucous leukoplakia (PVL) are oral potentially malignant disorders (OPMDs) that microscopically show no or varying degrees of dysplasia. Even sharing clinical and microscopic aspects, PVL shows a more aggressive clinical behaviour, with a malignant transformation rate greater than 40%. Inflammatory infiltrate associated with dysplastic lesions may favour malignant transformation of OPMDs. This study aimed to evaluate the density of T cells and cytokines in dysplastic lesions from OL and PVL patients. Additionally, we evaluated whether soluble products produced in vitro by dysplastic keratinocytes are capable of modulating apoptosis rates and Th phenotype (Th1, Th2, Th17 and Treg) of peripheral blood mononuclear cells. The density of CD3, CD4 and CD8 T cells was assessed by immunohistochemistry. Cytokines and chemokines profile from frozen tissue samples were analysed using the LUMINEX system. Apoptosis rates and Th phenotype modulation were evaluated by flow cytometry. Our results showed an increase in the number of CD8 T cell in the subepithelial region from PVL dysplastic lesions in relation to OL samples. PVL showed increased levels of IL-5 and a decrease in IL-1β and IFN-γ levels compared to OL. Soluble products of PVL and oral carcinoma cell cultures were able to reduce apoptosis rate and promote an imbalance of Th1/Th2 and Th17/Treg. The high-subepithelial density of CD8 T cells and immune imbalance of T lymphocytes subsets probably play an important role in the pathogenesis of PVL and may explain its more aggressive behaviour in relation to OL.
口腔白斑（OL）和增殖性疣状白斑（PVL）是口腔潜在恶性疾病（OPMDs），显微镜下表现为无发育异常或不同程度的发育异常。即使在临床和显微镜方面有共同之处，PVL的临床行为更具侵袭性，恶性转化率大于40%。与发育异常病变相关的炎症浸润可能有利于OPMDs的恶性转化。本研究旨在评估OL和PVL患者发育异常病变中T细胞和细胞因子的密度。此外，我们评估了发育异常角质形成细胞在体外产生的可溶性产物是否能够调节外周血单个核细胞的凋亡率和Th表型（Th1、Th2、Th17和Treg）。通过免疫组织化学评估CD3、CD4和CD8 T细胞的密度。使用LUMINEX系统分析冷冻组织样本中的细胞因子和趋化因子谱。通过流式细胞术评估凋亡率和Th表型调节。我们的结果显示，与OL样本相比，PVL发育异常病变上皮下区域的CD8 T细胞数量增加。与OL相比，PVL的IL-5水平升高，IL-1β和IFN-γ水平降低。PVL和口腔癌细胞培养物的可溶性产物能够降低凋亡率，并促进Th1/Th2和Th17/Treg的失衡。CD8 T细胞的高上皮下密度和T淋巴细胞亚群的免疫失衡可能在PVL的发病机制中起重要作用，并可能解释其相对于OL更具侵袭性的行为。
