Department of Oral Medicine and Pathology, School of Dentistry, National and Kapodistrian University of Athens, Greece.
Department of Oral and Maxillofacial Surgery, "Evaggelismos" General Hospital, National and Kapodistrian University of Athens, Greece.
Oral Surg Oral Med Oral Pathol Oral Radiol. 2020 May;129(5):493-513. doi: 10.1016/j.oooo.2020.01.001. Epub 2020 Mar 13.
Toll-like receptors (TLRs) may promote or inhibit tumor progression. The aim of this study was to assess the expression of TLR4 and TLR9 and their downstream targets in oral tongue squamous cell carcinoma (OTSCC) in correlation with histopathologic parameters and human papillomavirus (HPV) status.
OTSCC (fully or superficially invasive and in situ) were studied. Immunohistochemical expression of TLR4, TLR9, nuclear factor-κΒ (NF-κΒ/p65), and interferon-β (IFN-β) was evaluated in tumor and inflammatory cells and in adjacent morphologically normal mucosa. HPV status was also determined.
TLR4 showed increased expression levels in tumor and infiltrating inflammatory cells compared with adjacent mucosa, especially in fully invasive cases; a negative correlation between TLR4 levels in inflammatory cells and tumor grade was observed. TLR9 was upregulated in tumor and infiltrating inflammatory cells compared with the adjacent mucosa; its expression in inflammatory cells was higher in well differentiated tumors. NF-κΒ and IFN-β were elevated in cancerous tissues, especially in fully invasive cases, and positively correlated with TLR4 and/or TLR9. HPV positivity (detected in 15.9% of the cases) demonstrated positive correlation with TLR9 and NF-κΒ levels.
TLR4 and TLR9 are upregulated in OTSCC and its microenvironment and, by affecting important downstream molecules, such as NF-κB and IFN-β, may play a role in oral cancer development and progression.
Toll 样受体（TLRs）可能促进或抑制肿瘤的进展。本研究旨在评估 TLR4 和 TLR9 及其下游靶标在口腔舌鳞状细胞癌（OTSCC）中的表达情况，并与组织病理学参数和人乳头瘤病毒（HPV）状态相关联。
研究了 OTSCC（完全或浅表浸润性和原位）。在肿瘤和炎症细胞以及相邻形态正常的黏膜中评估了 TLR4、TLR9、核因子-κB（NF-κB/p65）和干扰素-β（IFN-β）的免疫组织化学表达。还确定了 HPV 状态。
与相邻黏膜相比，TLR4 在肿瘤和浸润性炎症细胞中的表达水平升高，尤其是在完全浸润性病例中；炎症细胞中 TLR4 水平与肿瘤分级呈负相关。与相邻黏膜相比，TLR9 在肿瘤和浸润性炎症细胞中上调；在分化良好的肿瘤中，其在炎症细胞中的表达更高。NF-κB 和 IFN-β 在癌组织中升高，尤其是在完全浸润性病例中，并且与 TLR4 和/或 TLR9 呈正相关。HPV 阳性（在 15.9%的病例中检测到）与 TLR9 和 NF-κB 水平呈正相关。
TLR4 和 TLR9 在 OTSCC 及其微环境中上调，并通过影响重要的下游分子，如 NF-κB 和 IFN-β，可能在口腔癌的发生和发展中发挥作用。
