Salivary Immunosuppressive Cytokines IL-10 and IL-13 Are Significantly Elevated in Oral Squamous Cell Carcinoma Patients

Aziz, Shuokr Qarani; Ahmed, Syed Shoaib; Ali, Ashhar; Khan, Faiza; Zulfiqar, Gulraiz; Iqbal, Javed; Khan, Ayyaz Ali; Shoaib, Muhammad

doi:10.3109/07357907.2015.1041642

Cited by 79 publications

(81 citation statements)

References 56 publications

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“…Of note, the levels of IL-10 and IL-13 were significantly increased, whereas the level of IL-1RA was the highest in poorly differentiated OSCC lesions compared with well- and moderately differentiated OSCC lesions. 19 A similar study found that the levels of TNF-α were higher in moderately and poorly differentiated tumours than in well-differentiated and stage IV tumours. Moreover, there was also a positive correlation between the histological grading of OSCC and TNF-α.…”

Section: Diagnosis Of Oral Diseases By Salivamentioning

confidence: 84%

Saliva in the diagnosis of diseases

et al. 2016

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Saliva is secreted from the salivary glands and has multiple functions, including mouth cleaning and protection, antibacterial effects and digestion. With the rapid advancement in salivaomics, saliva is well recognized as a pool of biological markers. Saliva, as a non-invasive and safe source, could be a substitute for blood in the diagnosis and prognosis of diseases. This review summarizes the latest advancements in saliva-related studies and addresses the potential value of saliva in the early diagnosis of oral diseases, such as dental caries and periodontal disease, as well as cancer, diabetes and other systemic disorders. Saliva biomarkers range from changes in the biochemical indices of DNA, RNA and proteins to the diversification of microbiota structures. This study integrates data reported in the recent literature and discusses the clinical significance and prospects for the application of saliva in the early diagnosis of diseases, translational medicine and precision medicine.

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Section: Diagnosis Of Oral Diseases By Salivamentioning

confidence: 84%

Saliva in the diagnosis of diseases

et al. 2016

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“…High expression of IL-6 in OSCC cells has been suggested as a predictive factor of poor response to chemoradiotherapy (31). The anti-inflammatory cytokine IL-1RA, which competes with IL-1β by binding to the IL-1 receptor, is also found in elevated levels in the saliva of patients with OSCC (32). IL-1β is secreted by tumor cells and is a substrate of MMP9 (10).…”

Section: Discussionmentioning

confidence: 99%

Matrix metalloproteinase (MMP) and immunosuppressive biomarker profiles of seven head and neck squamous cell carcinoma (HNSCC) cell lines

Bates¹,

Hernandez²,

Lanzel³

et al. 2018

Transl. Cancer Res

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Background: Biomarkers like programmed death ligand-1 (PDL1) have become a focal point for immunotherapeutic checkpoint inhibition in head and neck squamous cell carcinoma (HNSCC). However, it’s only part of the total immunosuppressive biomarker profile of HNSCC cells. Matrix metalloproteinases (MMPs) are enzymes that break down the basement membrane allowing cancer cells to metastasize and play an important role in the tumor microenvironment. MMPs can also activate certain cytokines, growth factors, and chemokines post-translationally. The objective of this study was to determine MMP and biomarker profiles of seven different HNSCC cell lines. Methods: Authenticated cell lines were grown in minimal media at 1×106 viable cells/mL and incubated at 37 °C. After 24 hrs supernatants were collected, and adhering cells were lysed. Multiplex immunoassays were used to determine MMP1, MMP7, MMP9, IL-6, VEGFA, IL-1α, TNF-α, GM-CSF, IL-1RA, and IL-8 concentrations in supernatants. ELISAs were used to determine PDL1, CD47, FASL, and IDO concentrations in cell lysates. A one-way ANOVA was fit to examine log-transformed concentrations of biomarkers between seven HNSCC cell lines, and pairwise group comparisons were conducted using post- hoc Tukey’s honest significance test (α=0.05). Results: Significant differences (P<0.05) in MMP and biomarker concentrations were found between the seven HNSCC cell lines. For example, MMP9 was highest in SCC25 and UM-SCC99, MMP7 was highest in SCC25 and UM-SCC19, and MMP1 was highest in SCC25. Conclusions: These results suggest different patients’ HNSCC cells can express distinct profiles of select biomarkers and MMPs, which could be due to metastatic stage of the cancer, primary tumor site, type of tissue the tumor originated from, or genomic differences between patients. MMP and biomarker expression profiles should be considered when choosing cell lines for future studies. The results support the reason for personalized medicine and the need to further investigate how it can be used to treat HNSCC.

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“…48 IL10 is found in elevated levels in the saliva of patients with HNSCC and may impair dendritic cell function and protect tumor cells from cytotoxic T-cells. 38,49,50 LGALS9 encodes for galectin-9, which is associated with metastasis and immunosuppression and found in elevated levels of lung, kidney, liver, and breast carcinomas. 51 Galectin-9 has been suggested to play a role in tumor cell evasion by inducing apoptosis in Th1 cells and cytotoxic T-cells.…”

Section: Discussionmentioning

confidence: 99%

Cell genomics and immunosuppressive biomarker expression influence PD-L1 immunotherapy treatment responses in HNSCC—a computational study

Bates

Lanzel

Qian

et al. 2017

Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology

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Objectives PD-L1 expression is correlated with objective responses rates (ORR) to PD-1 and D-L1 immunotherapies. However, both immunotherapies have only demonstrated 12.0–24.8% ORR in patients with HNSCC showing a need for a more accurate method to identify those who will respond prior to their therapy. Immunohistochemistry to detect PD-L1 reactivity in tumors can be challenging and additional methods are needed to predict and confirm PD-L1 expression. Here, we hypothesized that HNSCC tumor cell genomics influences cell signaling and downstream effects on immunosuppressive biomarkers and that these profiles can predict patient clinical responses. Study Design We identified deleterious gene mutations in SCC4, SCC15, and SCC25 and created cell line-specific predictive computational simulation models. The expression of 24 immunosuppressive biomarkers were then predicted and used to sort cell lines into those that would or would not respond to PD-L1 immunotherapy. Results SCC15 and SCC25 were identified as cell lines that would respond to PD-L1 immunotherapy treatment and SCC4 was identified as a cell line that would not likely respond to PD-L1 immunotherapy treatment. Conclusions This approach, when applied to patient HNSCC cancer cells, has the ability to predict PD-L1 expression and predict PD-1 or PD-L1 targeted treatment responses in those patients.

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Salivary Immunosuppressive Cytokines IL-10 and IL-13 Are Significantly Elevated in Oral Squamous Cell Carcinoma Patients

Cited by 79 publications

References 56 publications

Saliva in the diagnosis of diseases

Saliva in the diagnosis of diseases

Matrix metalloproteinase (MMP) and immunosuppressive biomarker profiles of seven head and neck squamous cell carcinoma (HNSCC) cell lines

Cell genomics and immunosuppressive biomarker expression influence PD-L1 immunotherapy treatment responses in HNSCC—a computational study

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