The tumor microenvironment (TME) is comprised of many different cell populations, such as cancer-associated fibroblasts and various infiltrating immune cells, and non-cell components of extracellular matrix. These crucial parts of the surrounding stroma can function as both positive and negative regulators of all hallmarks of cancer development, including evasion of apoptosis, induction of angiogenesis, deregulation of the energy metabolism, resistance to the immune detection and destruction, and activation of invasion and metastasis. This review represents a summary of recent studies focusing on describing these effects of microenvironment on initiation and progression of the head and neck squamous cell carcinoma, focusing on oral squamous cell carcinoma, since it is becoming clear that an investigation of differences in stromal composition of the head and neck squamous cell carcinoma microenvironment and their impact on cancer development and progression may help better understand the mechanisms behind different responses to therapy and help define possible targets for clinical intervention.

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Effect of tumor microenvironment on pathogenesis of the head and neck squamous cell carcinoma: a systematic review

Adipose tissue in addition to its ability to keep lipids is now recognized as a real organ with both metabolic and endocrine functions. Recent studies demonstrated that in obese animals is established a status of adipocyte hypoxia and in this hypoxic state interaction between adipocytes and stromal vascular cells contribute to tumor development and progression. In several tumors such as breast, colon, liver and prostate, obesity represents a poor predictor of clinical outcomes. Dysfunctional adipose tissue in obesity releases a disturbed profile of adipokines with elevated levels of pro-inflammatory factors and a consequent alteration of key signaling mediators which may be an active local player in establishing the peritumoral environment promoting tumor growth and progression. Therefore, adipose tissue hypoxia might contribute to cancer risk in the obese population. To date the precise mechanisms behind this obesity-cancer link is not yet fully understood. In the light of information provided in this review that aims to identify the key mechanisms underlying the link between obesity and cancer we support that inflammatory state specific of obesity may be important in obesity-cancer link.

/pdf/obesity-and-cancer-the-role-of-adipose-tissue-and-adipo-1tf0ofp1bm.pdf

Obesity and cancer: the role of adipose tissue and adipo-cytokines-induced chronic inflammation

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.

https://www.mdpi.com/2075-4418/7/2/21/pdf

Salivary IL-8, IL-6 and TNF-α as Potential Diagnostic Biomarkers for Oral Cancer.

Oral lichen planus (OLP) is a chronic inflammatory disease of unknown etiology with significant impact on patients' quality of life. Malignant transformation into oral squamous cell carcinoma (OSCC) is considered as one of the most serious complications of the disease; nevertheless, controversy still persists. Various factors seem to be involved in the progression of malignant transformation; however, the mechanism of this process is not fully understood yet. Molecular alterations detected in OLP samples might represent useful biomarkers for predicting and monitoring the malignant progression. In this review, we discuss various studies which highlight different molecules as ominous predictors of OLP malignant transformation.

/pdf/markers-of-oral-lichen-planus-malignant-transformation-4n1c4ev570.pdf

Markers of Oral Lichen Planus Malignant Transformation

Background: Oral squamous cell carcinoma (OSCC) is an important malignancy throughout the world; early detection is an important criterion for achieving high cure rate. Out of the many reported markers for OSCC, this study validated the efficacy of tumor necrosis factor-α (TNF- α) in differentially diagnosing premalignant oral lesions and OSCC. Also, the study aimed to correlate the levels of salivary and serum TNFα with clinicopathologic factors. Materials and Methods: A prospective experimental laboratory study was designed. Serum and salivary samples from 100 subjects in each group of healthy control, premalignant disease (PMD) and OSCC were collected for the study following appropriate exclusion and inclusion criteria. Serum and salivary level of TNF-α was analysed by enzyme linked immunosorbent assay. The data obtained were subjected to appropriate statistical analysis. Results: Increased level of both serum and salivary TNF- α was observed in OSCC subjects compared to healthy control and PMD group. Receiver operator characteristic curve analysis and area under curve values showed high specificity and sensitivity for salivary TNF-α in differentiating OSCC from PMD and healthy controls. There was significant increase in TNF- α level in moderately and poorly differentiated lesion compared to well differentiated lesion and in stage IV of clinical stage. A positive correlation was observed only with histological grading of OSCC and TNF- α. Conclusions: Salivary TNF-α is proved to be superior for detecting OSCC. Increase in TNF-α with histological grading and clinical staging suggests a role in prognosis.

http://koreascience.or.kr:80/article/JAKO201429765166808.pdf

Association of serum and salivary tumor necrosis factor-α with histological grading in oral cancer and its role in differentiating premalignant and malignant oral disease.

The aim of this study was to determine the salivary concentrations of tumour necrosis factor α (TNF-α) and interleukin 6 (IL-6) in patients with premalignant and malignant lesions. The study involved 57 patients who were examined between 2008 and 2010 at the Department of Oral Medicine and Department of Oral and Maxillofacial Surgery of the Medical Faculty, University of Rijeka, Croatia. They were divided into three groups: 19 patients with oral premalignant lesions, 19 with oral squamous cell carcinoma and 19 healthy control volunteers. Whole saliva was collected and investigated for the presence of TNF-α and IL-6 by enzyme immunoassay at the Department of Dentistry and Maxillofacial Surgery, Medical Faculty, University of Graz, Austria. All groups had statistically significant differences in values of TNF-α and IL-6 (P < 0.001). The results suggest that these proinflammatory cytokines are elevated in the saliva of patients with oral squamous cell carcinoma and oral premalignant lesions as compared to controls, which may have diagnostic and/or prognostic significance.

I Brekalo Pršo

Papers

Salivary levels of TNF-α and IL-6 in patients with oral premalignant and malignant lesions.