Department of Oral Pathology, Radiology, and Medicine, College of Dentistry, University of Iowa, Iowa City, IA, United States.
Department of Pathology, College of Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA, United States.
BMC Cancer. 2024 Jun 26;24(1):766. doi: 10.1186/s12885-024-12539-5.
In oral squamous cell carcinoma (OSCC), the tumor-node-metastasis (TNM) staging system is a significant factor that influences prognosis and treatment decisions for OSCC patients. Unfortunately, TNM staging does not consistently predict patient prognosis and patients with identical clinicopathological characteristics may have vastly different survival outcomes. Host immunity plays an important role in tumor progression but is not included in the TNM staging system. Tumor-infiltrating lymphocytes (TILs) are part of the host immune response that recognizes tumor cells; and the presence of TILs has emerged as potential candidates for prognostic markers for many types of cancers. The present study aims to determine the association of T cell-specific markers (CD3, CD4, CD8, and FOXP3) with clinicopathological characteristics and survival outcomes in OSCC patients. The prognostic value of CD3, CD4, and CD8 will also be evaluated based on tumor stage.
Tissue microarrays were constructed containing 231 OSCC cases and analyzed by immunohistochemical staining for the expression of CD3, CD4, CD8, and FOXP3. The expression scores for each marker were correlated with clinicopathological parameters and survival outcomes. The prognostic impact of CD3, CD4 and CD8 were further analyzed based on tumor stage (early or advanced).
CD3, CD4, and CD8 were found to be significantly associated with both overall survival and progression-free survival using univariate analysis. However, none of these markers were found to independently predict the survival outcomes of OSCC using multivariate analysis. Only conventional factors such as nodal status, tumor differentiation and perineural invasion (PNI) were independent predictors of survival outcomes, with nodal status being the strongest independent predictor. Additionally, low CD4 (but not CD3 or CD8) expression was found to identify early-stage OSCC patients with exceptionally poor prognosis which was similar to that of advanced staged OSCC patients.
TIL markers such as CD3, CD4, CD8, and FOXP3 can predict the survival outcomes of OSCC patients, but do not serve as independent prognostic markers as found with conventional factors (i.e. nodal status, tumor differentiation and PNI). CD4 expression may assist with risk stratification in early-stage OSCC patients which may influence treatment planning and decision making for early-stage OSCC patients.
在口腔鳞状细胞癌（OSCC）中，肿瘤-淋巴结-转移（TNM）分期系统是影响 OSCC 患者预后和治疗决策的重要因素。不幸的是，TNM 分期并不能始终预测患者的预后，具有相同临床病理特征的患者可能有截然不同的生存结果。宿主免疫在肿瘤进展中起着重要作用，但不包括在 TNM 分期系统中。肿瘤浸润淋巴细胞（TIL）是宿主免疫反应的一部分，可识别肿瘤细胞；TIL 的存在已成为许多类型癌症的潜在预后标志物候选者。本研究旨在确定 T 细胞特异性标志物（CD3、CD4、CD8 和 FOXP3）与 OSCC 患者的临床病理特征和生存结果的相关性。还将根据肿瘤分期评估 CD3、CD4 和 CD8 的预后价值。
构建包含 231 例 OSCC 病例的组织微阵列，并通过免疫组织化学染色分析 CD3、CD4、CD8 和 FOXP3 的表达。对每个标志物的表达评分与临床病理参数和生存结果进行相关性分析。根据肿瘤分期（早期或晚期）进一步分析 CD3、CD4 和 CD8 的预后影响。
使用单因素分析发现 CD3、CD4 和 CD8 与总生存和无进展生存均显著相关。然而，多因素分析并未发现这些标志物中的任何一种可独立预测 OSCC 的生存结果。只有淋巴结状态、肿瘤分化和神经周围浸润（PNI）等常规因素是生存结果的独立预测因素，淋巴结状态是最强的独立预测因素。此外，发现低 CD4（而不是 CD3 或 CD8）表达可识别出具有异常差预后的早期 OSCC 患者，其预后与晚期 OSCC 患者相似。
TIL 标志物（如 CD3、CD4、CD8 和 FOXP3）可预测 OSCC 患者的生存结果，但不能像常规因素（即淋巴结状态、肿瘤分化和 PNI）那样作为独立的预后标志物。CD4 表达可能有助于早期 OSCC 患者的风险分层，这可能影响早期 OSCC 患者的治疗计划和决策。
