Immunosuppressive mediators of oral squamous cell carcinoma in tumour samples and saliva

Gonçalves, Andréia Souza; Arantes, Diego Antônio Costa; Bernardes, Vanessa Fátima; Jaeger, Filipe; Silva, Janine Mayra da; Silva, Tarcı́lia Aparecida; Aguiar, Maria Cássia Ferreira de; Batista, Aline Carvalho

doi:10.1016/j.humimm.2014.11.002

Cited by 45 publications

(44 citation statements)

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“…Moreover, IL-10 concentration in saliva was higher than in serum. Goncalves et al [22] detected high expression of IL-10 in the tumour samples and elevated levels of this cytokine in saliva of patients with OSCC, which enabled to distinguish patients with cancer from healthy individuals. Jiang et al [23] additionally studied correlation between IL-10 and advancing cancer lesions on animal models.…”

Section: Discussionmentioning

confidence: 99%

Salivary and serum IL-10, TNF-α, TGF-β, VEGF levels in oropharyngeal squamous cell carcinoma and correlation with HPV and EBV infections

Polz‐Dacewicz

Strycharz-Dudziak

Dworzański

et al. 2016

Infect Agents Cancer

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BackgroundEach year approximately 6,000 new cases of head and neck cancer are registered in Poland. Human papillomavirus (HPV) and Epstein-Barr virus (EBV) have been associated with tumour formation. Cytokines have been shown to play an important role both in inflammation and carcinogenesis and they can be detected in saliva and serum with ELISA assays. Salivary biomarkers may be used as markers of early cancer detection.The aim of this study was the analysis of the serum and salivary levels of IL-10, TNF-α, TGF-β and VEGF in patients with oropharyngeal cancer and in healthy individuals. The level of these biomarkers was also analyzed in HPV- and EBV-related cases.MethodsThe study involved 78 patients with histopathologically confirmed oropharyngeal squamous cell carcinoma and 40 healthy controls. Serum and salivary levels of IL-10, TNF-α, TGF-β and VEGF were analyzed both in patients and in healthy individuals by ELISA method using Diaclone SAS commercially available kits (France). EBV DNA was detected by the nested PCR for amplification of EBNA-2. HPV detection and genotyping was performed using the INNO-LiPA HPV Genotyping Extraassay (Innogenetics N. V, Gent, Belgium). The obtained results were subjected to statistical analysis using Mann–Whitney and Kruskal Wallis tests. Test values of p < 0.05 were considered statistically significant.ResultsThe level of tested cytokines was higher in patients than in controls both in serum (IL-10: 2.3 pg/ml vs 1.65 pg/ml, p = 0.0003; TGF-β: 11.3 ng/ml vs 7.8 ng/ml, p = 0.0005; VEGF: 614 pg/ml vs 210 pg/ml, p = 0.0004; TNF-α: 15.0 ng/ml vs 12.90 ng/ml, p = 0.1397) as well as in saliva (IL-10: 5.9 pg/ml vs 2.5 pg/ml, p = 0.00002; TGF-β: 24.1 ng/ml vs 14.8 ng/ml, p = 0.00002; VEGF: 4321 pg/ml vs 280 pg/ml, p = 0.0000; TNF-α: 23.1 ng/ml vs 11.3 ng/ml, p = 0.00002).EBV DNA was detected in 51.3 % of patients and 20 % of controls, HPV DNA was present in 30.8 % of patients and 2,5 % of controls.The level of IL-10 was statistically higher in patients infected with EBV, HPV and co-infected with EBV/HPV. The level of TNF-α was significantly higher in patients infected with EBV, while TGF-β in patients with HPV infection and EBV/HPV co-infection.ConclusionDetection of salivary cytokines may be very helpful in early diagnosis, treatment and prognosis of OSCC.

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Section: Discussionmentioning

confidence: 99%

Salivary and serum IL-10, TNF-α, TGF-β, VEGF levels in oropharyngeal squamous cell carcinoma and correlation with HPV and EBV infections

Polz‐Dacewicz

Strycharz-Dudziak

Dworzański

et al. 2016

Infect Agents Cancer

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“…Since persistent viral infection promotes IL-10 upregulation and impaired T-cell responses [56], it is believed that this cytokine plays a critical role in human papilloma virus (HPV)- and Epstein-Barr virus (EBV)-related OSCC progression [57, 58]. Moreover, IL-10 indicates poor outcomes in HPV-unrelated OSCC, especially when INF-γ secretion [59] and transforming growth factor beta 1 (TGF-β1) levels [60] are low. Receptors for IL-22, a member of the IL-10 family, are highly expressed in OSCC cells, including in metastatic sites, compared to healthy regions.…”

Section: Introductionmentioning

confidence: 99%

“…However, this methodology is time and cost demanding and probably unfeasible in clinical situations, especially in less developed countries where the prevalence of OSCC is higher. However, from the available evidence, it is possible to suggest that screening for TAM markers in oral biopsies certainly may contribute to accurate assessment of OSCC behaviour, being a valuable tool for the estimation of prognosis in cases related and unrelated to viral infection [57–60, 68]. …”

Section: Introductionmentioning

confidence: 99%

Role of tumour-associated macrophages in oral squamous cells carcinoma progression: an update on current knowledge

et al. 2017

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BackgroundOral squamous cell carcinoma (OSCC) accounts over 90% of malignant neoplasms of the oral cavity. This pathological entity is associated to a high mortality rate that has remained unchanged over the past decades. Tumour-associated macrophages (TAMs) are believed to have potential involvement in OSCC progression. However, the molecular networks involved in communication between stroma and cancer cells have not yet been fully elucidated.Main bodyThe role of M2 polarized cells in oral carcinogenesis is supported by a correlation between TAMs accumulation into OSCC stroma and poor clinical outcome. Signalling pathways such as the NF-κB and cytokines released in the tumour microenvironment promote a bidirectional cross-talk between M2 and OSCC cells. These interactions consequently result in an increased proliferation of malignant cells and enhances aggressiveness, thus reducing patients’ survival time.ConclusionsHere, we present a comprehensive review of the role of interleukin (IL)-1, IL-4, IL-6, IL-8, IL-10 and the receptor tyrosine kinase Axl in macrophage polarization to an M2 phenotype and OSCC progression. Understanding the molecular basis of oral carcinogenesis and metastatic spread of OSCC would promote the development of targeted treatment contributing to a more favourable prognosis.

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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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Immunosuppressive mediators of oral squamous cell carcinoma in tumour samples and saliva

Cited by 45 publications

References 46 publications

Salivary and serum IL-10, TNF-α, TGF-β, VEGF levels in oropharyngeal squamous cell carcinoma and correlation with HPV and EBV infections

Salivary and serum IL-10, TNF-α, TGF-β, VEGF levels in oropharyngeal squamous cell carcinoma and correlation with HPV and EBV infections

Role of tumour-associated macrophages in oral squamous cells carcinoma progression: an update on current knowledge

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

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