Tumour Necrosis Factor Alpha (TNF-α) and Oral Squamous Cell Carcinoma

Abstract

Uncovering the inflammatory mechanisms underpinning initiation, progression, and promotion of oral squamous cell carcinoma (OSCC) development is fundamental to the rational pursuit of targeted therapeutics. Here we present a review of the current knowledge of the role of TNF-α in the aetiology, pathogenesis, and potential therapies with regards to OSCC. TNF-α is worthy of particular attention in OSCC, with its presence demonstrated to enhance cell proliferation and its downregulation demonstrated to inhibit proliferation and migration in other carcinomas in both in vitro and in vivo models and oral cancer patients. Increased TNF-α in the OSCC tumour microenvironment has been demonstrated to favour invasion through promotion of firstly the pro-inflammatory, pro-invasive phenotypes of OSCC cells and secondly its paracrine mechanism mediating recruitment and activation of inflammatory cells. Polymorphisms affecting the gene expression of TNF-α have been strongly associated with an increased risk for oral squamous cell carcinoma. A number of studies have considered TNF-α within biofluids, including saliva and serum, as a potential biomarker for the early detection of OSCC, as well as its staging, differentiation, and prognosis. The broad and multifaceted role that TNF-α plays in many inflammatory states presents an obvious confounder, particularly with demonstrated increased TNF-α levels in common oral disease states. Lastly, biologic agents targeting TNF-α are currently in clinical use for immune-mediated inflammatory rheumatological and gastrointestinal diseases. There is the potential that these biological agents might have an adjunctive role in OSCC prevention and treatment.

Evaluating Tumor Necrosis Factor (TNF)-Alpha Pro-inflammatory Cytokines in Healthy and Oral Squamous Cell Carcinoma Patients With and Without Diabetes

“…This study aligns with existing research showing that TNF-α was highly expressed by patients with OSCC. Such an observation emphasizes the contribution that TNF-α may play in promoting oral carcinogenesis [9]. As shown by Brailo et al, patients with oral leukoplakia had significantly higher salivary levels of IL-6 and TNF-α compared to healthy controls [15].…”

“…TNF-α is of utmost importance due to its involvement in the causation of both OSCC and diabetes of type 2. TNF-α is a main contributor to the interaction among the abovementioned three pathologies [9]. TNF-α is a mediator that could help us understand how it impacts disease development specifically in OSCC among diabetic patients.…”

AIM2 promotes irradiation resistance, migration ability and PD-L1 expression through STAT1/NF-κB activation in oral squamous cell carcinoma

“…As a result, targeting NF-κB activity was thought to be a potential strategy to combat cancer radioresistance [ 30 ]. Recent reports demonstrated that the activation of the TNF-α/NF-κB signaling axis enhances the metastatic capacity and PD-L1 expression of OSCC [ 31 , 32 ]. Inhibition of NF-κB was found to mitigate the cellular invasive ability and restore the responsiveness to radiotherapy in glioblastoma [ 33 ].…”

“…fibroblast, can produce TNFα [ 40 ]. TNFα has been associated with the progression and prognosis of different cancer types by perturbing several signaling pathways, e.g., Erk1/2 and NF-κB [ 32 ]. Besides, TNFα coordinated with IFNγ to promote MUC16 (CA125) expression in breast and ovarian cancer via the NF-κB signaling axis [ 41 ].…”

Simvastatin Attenuates Areca Nut Extract-Induced Subdermal Fibrosis in Mice by Targeting TGF-β Signaling Pathways

“…Oral submucosal fibrosis (OSMF) is a disease affecting the oral mucosa, leading to restricted mouth opening and trismus [1]. OSMF is associated with poor oral hygiene and dysphagia and is considered a precursor to squamous cell carcinoma (SCC) [2]. The prevalence of OSMF is higher in the Asia-Pacific region and lower in Europe and the United States.…”