Impact of smoking on dendritic cells in patients with oral squamous cell carcinoma

Stähelin, Heron; Francisco, Ana Lúcia Noronha; Mariano, Fernanda Viviane; Kowalski, Luiz Paulo; Gondak, Rogério

doi:10.1590/1807-3107bor-2021.vol35.0075

“…Of note, a study based on genomic data has suggested that SD and NSND patients exhibit different transcriptomic profiles of TME ( 13 ) in line with our present results. The increase of CD45RO + CCR6 + CD4 + cells, IL-17 + cells and granulocytes in SD patients was significantly associated with a poor prognosis, although no difference in terms of the overall DFS between SD and NSND patients was observed, as already reported ( 28 – 30 ). Whether the increased presence of Th17 + cells is associated with a poor prognosis is still a matter of controversy.…”

Section: Discussionsupporting

confidence: 73%

Defining biomarkers in oral cancer according to smoking and drinking status

Rochefort

¹

,

Karagiannidis

²

,

Baillou

³

et al. 2023

Front. Oncol.

3

0

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IntroductionOral Squamous Cell Carcinomas (OSCC) are mostly related to tobacco consumption eventually associated to alcohol (Smoker/Drinker patients: SD), but 25-30% of the patients have no identified risk factors (Non-Smoker/Non-Drinker patients: NSND). We hypothesized that these patients have distinguishable immune profiles that could be useful for prognosis.Materials and MethodsCells present in immune tumor microenvironment (TME) and blood from 87 OSCC HPV-negative patients were analyzed using a multiparameter flow cytometry assay, in a prospective case-control study. Cytokine levels in tumor supernatants and blood were determined by a cytometric bead array (CBA) assay.ResultsNormal gingiva and blood from healthy donors (HD) were used as controls. A significant increase of granulocytes (p<0.05 for blood), of monocytes-macrophages (p<0.01 for blood) and of CD4+ T cells expressing CD45RO and CCR6 (p<0.001 for blood; p<0.0001 for TME) as well as higher levels of IL-6 (p<0.01 for sera, p<0.05 for tumor supernatant) were observed in SD patients as compared to NSND OSCC patients and HD. High percentages of CD4+ T cells expressing CD45RO and CCR6 cells in tumor tissue (p=0.05) and blood (p=0.05) of SD OSCC patients were also associated with a poorer prognosis while a high percentage of regulatory T cells (Treg) in tumor tissue was associated with a more favorable prognostic factor (p=0.05). Also, a higher percentage of blood CD8+ T lymphocytes among CD45+ cells in NSND patients was associated with a better disease-free survival (p=0.004).ConclusionGranulocytes, monocytes-macrophages, and CD4+ T cells expressing CD45RO and CCR6 in blood and TME as well as serum IL-6 can therefore distinguish OSCC SD and NSND patients. Quantifying the proportion of CD4+ T cells expressing CD45RO and CCR6 and of Treg in SD patients and CD8+ T cells in NSND patients could help defining the prognostic of OSCC patients.

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“…Thereby, the causality of the relationship or, in other words, whether T2D would be an independent predictor for OSCC formation and outcome can be discussed controversially [ 7 ]. An indirect link would also be plausible; on the one hand, a shared risk complex, i.e., nutrition, obesity, and smoking would also predict T2D as well as OSCC [ 15 – 19 ]. On the other hand, oral inflammations, especially periodontitis and mucous diseases, are related to T2D [ 4 , 20 ].…”

Section: Discussionmentioning

confidence: 99%

Genetic Cross-Talk between Oral Squamous Cell Carcinoma and Type 2 Diabetes: The Potential Role of Immunity

Fan

¹

,

Zhang

²

,

Shi

³

et al. 2022

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Background. This bioinformatics study was aimed at evaluating type 2 diabetes (T2D) and oral squamous cell carcinoma (OSCC) with regard to related immune cells and prognosis. Methods. We downloaded the data on OSCC from TCGA and for T2D from GEO database. Differentially expressed genes were analyzed, i.e., for OSCC genes with p value < 0.01 , log 2 FC > 0 ; and for T2D, genes with p value < 0.05 , log 2 FC > 0 . The intersected genes between OSCC and T2D were cross-talk genes. The expression values of immune-related genes in case samples in OSCC and T2D were assessed and underwent multivariate and univariate analysis (Cox-PH model). The intersection between the immune genes and cross-talk genes was taken and further analyzed by recursive feature elimination (RFE), survival analysis, and ROC analysis. Results. 1008 cross-talk genes were acquired, including 28 common upregulated, 440 common downregulated, and 540 differently regulated DEGs. We extracted the gene expression value of 782 immune-related genes, of which seven increased immune cells were obtained. From the results, plasmacytoid dendritic cells and effector memory CD8 T cells were highly negatively correlated in both OSCC and T2D. After estimating a low- and high-risk model for survival, we found that activated dendritic cell was significantly different between high and low groups ( p = 0.0095 ), followed by plasmacytoid dendritic cell. We integrated DE_Immune genes set 1 and DE_Immune genes set 2 and eight key immune-related cross-talk genes (C1QC, ABCD1, NOS2, PDIA4, IL1RN, ALOX15, CSE1L, and PSMC4) were evaluated. After ROC analysis, we obtained that ABCD1, C1QC, CSE1L, and PSMC4 had higher classification and prediction effects on OSCC and T2D. Conclusion. This study revealed a close relationship between T2D and OSCC. Thereby, plasmacytoid dendritic cell and activated dendritic cell-related genes were associated with the survival of T2D-related OSCC, while ABCD1, C1QC, CSE1L, and PSMC4 were the most important immune-related cross-talk genes.

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OSCC in Never-Smokers and Never-Drinkers Is Associated with Increased Expression of Tumor-Infiltrating Lymphocytes and Better Survival

Fiedler,

Off,

Eichberger

et al. 2023

Cancers

0

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The aim of this study was to investigate the clinical, histopathologic, and immunologic differences of oral squamous cell carcinoma of never-smokers/never-drinkers and smokers/drinkers. Immunohistochemical staining for CD4, CD8, FoxP3, CD1a, and p16 was performed in 131 oral squamous cell carcinomas from smokers/drinkers and never-smokers/never-drinkers. Associations of smoking/drinking status with clinicopathologic data, immunohistochemical antibody expression, and survival were examined. Oral squamous cell carcinoma in never-smokers/never-drinkers was associated with the female gender (p < 0.001). Never-smokers/never-drinkers were older at diagnosis than smokers/drinkers (p < 0.001). Never-smokers/never-drinkers had more tumors in the maxilla, mandible, and tongue (p < 0.001). Pre-existing oral potentially malignant disorders appeared to be more common in never-smokers/never-drinkers (p < 0.001). Perineural invasion was more common in smokers/drinkers (p = 0.039). Never-smoking/never-drinking was associated with better overall survival (p = 0.004) and disease-specific survival (p = 0.029). High CD4+ T cell infiltration was associated with never-smoking/never-drinking (p = 0.008). Never-smokers/never-drinkers also showed increased CD8+ T cell infiltration (p = 0.001) and increased FoxP3+ Treg infiltration (p = 0.023). Furthermore, the total group of tumor-infiltrating lymphocytes was associated with never smoking/never drinking (p = 0.005). To conclude oral squamous cell carcinoma of the never-smokers/never-drinkers appears to be a distinct type of tumor, as it appears to have unique clinical and pathologic features and a more immunogenic microenvironment.

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Impact of smoking on dendritic cells in patients with oral squamous cell carcinoma

Cited by 3 publications

References 39 publications

Defining biomarkers in oral cancer according to smoking and drinking status

Defining biomarkers in oral cancer according to smoking and drinking status

Genetic Cross-Talk between Oral Squamous Cell Carcinoma and Type 2 Diabetes: The Potential Role of Immunity

OSCC in Never-Smokers and Never-Drinkers Is Associated with Increased Expression of Tumor-Infiltrating Lymphocytes and Better Survival

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