Defining biomarkers in oral cancer according to smoking and drinking status
Résumé
Introduction Oral 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 Methods Cells 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. Results Normal 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). Conclusion Granulocytes, 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.
Mots clés
oral cancer prognostic biomarker tumor microenvironment oral squamous cell carcinoma non-smoker non-drinker
oral cancer
prognostic biomarker
tumor microenvironment
oral squamous cell carcinoma
non-smoker
non-drinker
oral cancer prognostic biomarker tumor microenvironment oral squamous cell carcinoma non-smoker non-drinker
Domaines
Sciences du Vivant [q-bio]Origine | Fichiers éditeurs autorisés sur une archive ouverte |
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