Universidade Federal de Jataí, Curso de Medicina, Jataí, Goiás, Brasil.
Universidade Federal de Jataí, Ambulatório de Diagnóstico Estomatológico do Sudoeste Goiano (ADESGO), Jataí, Goiás, Brasil.
J Appl Oral Sci. 2022 Feb 21;30:e20210344. doi: 10.1590/1678-7757-2021-0344. eCollection 2022.
Lower lip squamous cell carcinomas (LLSCC) could be associated with a previous history of potentially malignant oral diseases (PMOD), especially actinic cheilitis (AC), with high sun exposure being a well-described risk factor. Immune evasion mechanisms, such as the PD-1/PD-L1 (programmed cell death protein 1/programmed death-ligand 1) pathway has been gaining prominence since immunotherapy with immune checkpoint inhibitors showed a positive effect on the survival of patients with different types of neoplasms. Concomitant with the characterization of the tumor microenvironment, the expression of either or both PD-1 and PD-L1 molecules may estimate mutual relations of progression or regression of the carcinoma and prognostic values of the patient.Considering the importance of tumor microenvironment characterization, this study aims to determine the immunoexpression of PD-L1 and correlate with the frequency of CD4+ and CD8+ cells in AC and LLSCC lesions and with tumor-infiltrating lymphocytes (TILs) in LLSCC and its relationship with histopathological characteristics.
This sample includes 33 cases of AC and 17 cases of LLSCC. The cases were submitted to histopathological analysis and to CD4+, CD8+, and PD-L1+ cell determination by immunohistochemistry.
There was a significant difference among the frequencies of CD4+, CD8+, and PD-L1+ cells between AC and LSCC cases, higher in the last group. Moreover, histopathological and atypical changes in AC and LLSCC were correlated with the frequencies of PD-L1+, CD4+, and CD8+ cells. In AC, PD-L1+ cases had a low frequency of CD4+ cells, but on the other hand, PD-L1+ cases of LLSCC had a higher frequency of CD4+ and CD8+ cells.
Therefore, the PD-L1 molecule may be a potential escape route for the immune response in oral lesions, but the mechanisms differ between AC and LLSCC. Future studies related to immune evasion and immunotherapy in oral lesions should consider the analysis of inflammatory infiltrate and TILs.
下唇鳞状细胞癌（LLSCC）可能与潜在恶性口腔疾病（PMOD）有关，尤其是光化性唇炎（AC），高阳光暴露是一个众所周知的危险因素。免疫逃逸机制，如 PD-1/PD-L1（程序性细胞死亡蛋白 1/程序性死亡配体 1）途径，由于免疫检查点抑制剂的免疫疗法显示对不同类型肿瘤患者的生存有积极影响，因此越来越受到关注。随着肿瘤微环境特征的描述，PD-1 和 PD-L1 分子的表达可以估计癌的进展或消退的相互关系以及患者的预后价值。考虑到肿瘤微环境特征的重要性，本研究旨在确定 PD-L1 的免疫表达，并与 AC 和 LLSCC 病变中 CD4+和 CD8+细胞的频率以及 LLSCC 中的肿瘤浸润淋巴细胞（TIL）及其与组织病理学特征的关系相关联。
本样本包括 33 例 AC 和 17 例 LLSCC。对病例进行组织病理学分析，并通过免疫组织化学法确定 CD4+、CD8+和 PD-L1+细胞。
AC 和 LSCC 病例之间 CD4+、CD8+和 PD-L1+细胞的频率存在显著差异，后者更高。此外，AC 和 LLSCC 的组织病理学和非典型改变与 PD-L1+、CD4+和 CD8+细胞的频率相关。在 AC 中，PD-L1+病例的 CD4+细胞频率较低，但另一方面，LLSCC 的 PD-L1+病例的 CD4+和 CD8+细胞频率较高。
因此，PD-L1 分子可能是口腔病变中免疫反应的潜在逃逸途径，但 AC 和 LLSCC 之间的机制不同。未来与口腔病变中的免疫逃逸和免疫疗法相关的研究应考虑炎症浸润和 TIL 的分析。
