Immunosuppressive mediators of oral squamous cell carcinoma in tumour samples and saliva (original) (raw)
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Oral squamous cell carcinoma (OSCC) is considered to be one of the most fatal diseases worldwide, owing to its late diagnosis and lack of availability of established reliable biomarkers. The aim of this study was to highlight the significance of immunosuppressive cytokines as potential biomarkers in OSCC. Whole unstimulated saliva was collected from each individual (30 OSCC patients and 33 age-and gender-matched healthy controls). Immunosuppressive cytokines, including IL-4, IL-10, IL-13, and IL-1RA, were evaluated in each sample using Luminex multianalyte profiling (xMAP) technology on BioPlex instrument. Our results showed that all the studied salivary cytokines were raised in OSCC patients as compared to controls, where IL-10 and IL-13 salivary levels showed statistically significant difference (p = .004 and p = .010, respectively). Mean levels of salivary cytokines in three histologically defined OSCC categories, compared employing one-way ANOVA, showed that salivary levels of IL-1RA were highest in patients having poorly differentiated OSCC tumors as compared to those having moderately and well-differentiated tumors (p = .000 and p = .002, respectively). Among OSCC individuals, duration of smokeless tobacco correlated positively with IL-1RA (p = .036). We conclude that salivary levels of immunosuppressive cytokines, IL-4, IL-10, IL-13, and IL-1RA, could prove to be potential biomarkers of OSCC and can be further investigated as markers of early detection and disease progression.
Asian Pacific Journal of Cancer Prevention Apjcp, 2013
BACKGROUND: Head and neck SCC is a common cancer related to various factors. IL-10, a pleiotropic cytokine produced by macrophages, T-helper-2 cells, and B lymphocytes, is thought to play a potential pathogenetic or therapeutic role in a number of human conditions, such as inflammation, autoimmunity and cancer. The present study was designed to evaluate the relation between tissue expression, serum and salivary levels of IL-10 in head and neck squamous cell carcinomas (HNSCCs) and their correlation with clinicopathologic features.MATERIALS AND METHODS: Samples were collected from 30 patients with HNSCCs and 24 healthy volunteers. IHC analysis was used to examine the tissue expression and ELISA was employed to measure serum and salivary levels.RESULTS: Our study showed tissue expression of IL-10 to be significantily higher in patients (P: 0.001), but there was no relation between tissue expression , serum and salivary levels of the marker (P>0.05). Also except for a positive correlation between tissue expression of IL-10 and stage (P: 0.044), there was no relation between this marker and clinicopathologic features. There was no correlation between serum and salivary levels in either patients or controls.CONCLUSIONS: It seems there is no correlation between level of IL-10 in serum and saliva and this marker in saliva and serum does not reflect tissue expression.
Journal of Oral and Maxillofacial Pathology, 2012
Oral squamous cell carcinoma (OSCC) is the most common type of head and neck cancer. The 5-year survival rate has remained below 50% over the last two decades, and new tools for early diagnosis are needed. Saliva has been used for diagnosis of several systemic diseases, and its use for diagnosis of OSCC has been sought extensively. Among the many salivary analytes for diagnosis of OSCC, accumulating evidences indicate the possibility of using salivary cytokines. Overproduction of proinflammatory, proangiogenic cytokines by OSCC cells has been reported, and their role in tumor progression and angiogenesis is well established. However, many inflammatory conditions and immunological diseases could affect the levels of cytokines in serum and saliva. This article has reviewed publications in this matter, and some strengths and weaknesses have been pointed out. Conclusively, large-scale investigations are required for validation of the use of salivary cytokines for diagnosis of OSCC, with consideration to the influential role of periodontal inflammation in their levels.
Journal of Clinical Medicine
Background: Oral squamous cell carcinoma (OSCC) is a life-threatening disease. It could be preceded by oral potentially malignant disorders (OPMDs). It was confirmed that chronic inflammation can promote carcinogenesis. Cytokines play a crucial role in this process. The aim of the study was to evaluate interleukin-1alpha (IL-1α), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor alpha (TNF-α) in tissue specimens and saliva of patients with OSCC and OPMDs. Methods: Cytokines were evaluated in 60 tissue specimens of pathological lesions (OSCCs or OPMDs) and in 7 controls (normal oral mucosa, NOM) by immunohistochemistry and in saliva of 45 patients with OSCC or OPMDs and 9 controls (healthy volunteers) by enzyme-linked immunosorbent assays. Results: Immunohistochemical analysis revealed significantly higher expression of IL-8 in OSCC specimens and TNF-α in OSCCs and OPMDs with dysplasia as compared to NOM. Moreover, expression of TNF-α was significantly higher in o...
2014
The main purpose of this article is to develop a new and reliable saliva-based clinical diagnostic method for the early detection of oral squamous cell carcinoma (OSCC). This study used an immunoproteomic approach which allowed the detection of immunogenic host proteins in patients' samples using pooled human antibodies. In an attempt to investigate potential biomarkers of OSCC, two-dimensional electrophoresis (2-DE) followed by immunoblotting of saliva from patients and controls were compared. The protein spots of interest were analyzed using 2-DE image analyzer and subsequently subjected to MALDI-TOF/TOF and then matched against NCBI database. The result showed that four protein clusters, namely Human Pancreatic Alpha-amylase (HPA), Human Salivary Amylase (sAA), keratin-10 (K-10), and Ga Module Complexed with Human Serum Albumin (GA-HSA), had exhibited immunoreactivity in western blot. The results are suggestive of the potential use of the differentially expressed saliva protein as tumor biomarkers for the detection of OSCC. However, further studies are recommended to validate this finding.
Cancer Detection and Prevention, 2005
Previous investigations in our laboratory and others have shown that the levels of certain inflammatory, proangiogenic cytokines in saliva and tissue specimens of patients with oral premalignant lesions (OPML) are elevated. We have also shown that these cytokines are elevated in tissue culture of oral squamous cell carcinoma (OSCC) cell lines. The purpose of this pilot study was to determine the level of several inflammatory, NF-kB-dependent cytokines in whole unstimulated saliva (WUS), in subjects with OPML as compared to those with diagnosed OSCC. Subjects (n = 13) with OMPL, OSCC (n = 13), and age-sex matched controls without oral lesions (C) (n = 13) were enrolled. The mean age was 58.7 years. WUS was collected by standard techniques for 5 min (Navazesh, 1993). WUS samples were centrifuged and the cytokine analysis was performed on the supernatants by ELISA as previously described by Ondrey et al. (1991). The cytokines analyzed were: TNF-alpha, interleukin-1, interleukin-6, and interleukin-8 (TNF-a, IL-1, IL-6, and IL-8). The results as analyzed by Pairwise t-tests revealed significant differences in the salivary levels of: (1) TNF-a: (mean AE S.E.M.: TNF-a-OSSC = 28.9 AE 14.6 * pcg/ml versus OPML = 10.5 AE 7.4 * pcg/ml versus controls = 3.0 AE 1.0 pcg/ml; * p < 0.01); (2) IL-1: (IL-1-OSSC = 454.4 AE 215.8 * pcg/ml versus OPML = 255.1 AE 124.8 * pcg/ml versus controls = 173.2 AE 66.9 pcg/ml; * p < 0.01); (3) IL-6: (mean AE S.E.M.: IL-6-OSSC = 88.2 AE 43.2 * pcg/ml versus OPML = 70.8 AE 24.3 * pcg/ml versus controls = 1.4 AE 1.0 pcg/ml; * p < 0.001) and (4) IL-8 in saliva: (mean AE S.E.M.: IL-8-OSSC = 3154.1 AE 1023.2 * pcg/ml versus OPML = 1918.2 AE 899.1 * pcg/ml versus controls = 1580.7 AE 789.0 pcg/ml; * p < 0.001). There was a significant increase in the levels of all cytokines in the saliva of the OPML as compared to controls, and a significant difference in the cytokines of OSSC saliva compared to the OPML and controls. These results suggest that these proangiogenic, proinflammatory cytokines are elevated in the saliva of patients with OSSC and OPML as compared to controls, which may have diagnostic and/or prognostic significance. #
Immunology of Oral Squamous Cell Carcinoma—A Comprehensive Insight with Recent Concepts
Life
This review aims to understand the concept of oral cancer immunology through the notion of immune profiling, immunoediting and immunotherapy, and to gain knowledge regarding its application for the management of oral cancer patients. Oral cancer is an immunogenic tumor where the cells of the tumor microenvironment play an important role in tumorigenesis. Understanding the mechanism of these modulations can help design immunotherapeutic strategies in oral cancer patients. This article gives an overview of immunomodulation in the oral cancer tumor microenvironment, with concepts of immune profiling, immunoediting and immunotherapy. English literature searches via Google Scholar, Web of Science, EBSCO, Scopus, and PubMed database were performed with the key words immunology, tumor microenvironment, cells, cross talk, immune profiling, biomarkers, inflammation, gene expression, techniques, immunoediting, immunosurveillance, tumor escape, immunotherapy, immune checkpoint inhibitors, vacc...
Journal article, 2023
Simple Summary: The incidence of oral cancer is increasing with little improvement in survival. This is due to late diagnosis with most cases diagnosed at a stage beyond a cure. In Sri Lanka, oral cancer is the most common cancer in males, carrying a high mortality rate. Identifying markers that can help in early detection is important for improving patient outcome. Here, we present findings from a study in Sri Lanka that assessed salivary interleukins in oral cancer and precancer patients compared to disease-free controls. Our results clearly show that the salivary protein levels of these interleukins progressively increase from disease-free participants through different grades of dysplasia with the highest levels reported in cancer patients. This has significant clinical potential, as assessment of salivary levels of these interleukins can be developed into non-invasive risk assessment tools for detecting disease progression in dysplasia, and as screening tests for early detection of oral cancer.
Salivary IL-8, IL-6 and TNF-α as Potential Diagnostic Biomarkers for Oral Cancer
Diagnostics, 2017
Saliva has been useful as a liquid biopsy for the diagnosis of various oral or systemic diseases, and oral squamous cell carcinoma (OSCC) is no exception. While its early detection and prevention is important, salivary cytokines expression, specifically of Interleukin-8 (IL-8), Interleukin-6 (IL-6) and Tumor necrosis factor (TNF-α), does contribute to the pathogenesis of cancer and these cytokines serve as potential biomarkers. Their excessive production plays a role in cancer progression and establishment of angiogenesis. However, other inflammatory or immunological conditions may affect the levels of cytokines in saliva. This article reviews the expression of levels of specific cytokines i.e., IL-8, IL-6 and TNF-α, their signaling pathways in the development of oral cancer, and how they are essential for the diagnosis of OSCC and updates related to it. Apart from serum, the saliva-based test can be a cost-effective tool in the follow-up and diagnosis of OSCC. Moreover, large-scale investigations are still needed for the validation of salivary cytokines.
Cytokine, 2019
Salivary biomarkers represent a promising diagnostic tool. Non-invasive and stress-free sampling results in objective parameters able to overcome the need of clinical expertise required for a correct interpretation of early oral squamous cell carcinoma (OSCC). The present study aims at evaluating potential variations in the salivary concentration of cytokines in presence of OSCC. Twenty patients who underwent surgical resection of OSCC were enrolled in order to assess the variation of the salivary concentration of cytokines and chemokines in a longitudinal prospective case-crossover setting. The salivary concentration of 27 salivary cytokines/chemokines was assessed before and after surgical resection of OSCC. In cases of relapsing/recurrent disease further assessments were performed. In presence of OSCC an increased concentration of IL-8(p = 0.004), IL-6(p = 0.005), VEGF(p = 0.014), MIP-1ß(p = 0.033), IP-10(p = 0.047), IL-1β(p = 0.049) was observed; conversely the concentration of IFNγ(p = 0.036) and IL-5(P = 0.048) decreased. In cases with relapsing/recurrent disease IL-5, IL-6 and MIP-1β showed variations consistent with the previously reported results. Further studies are needed in order to confirm these results and to determine reference values to determine the presence or absence of disease.