Defining biomarkers in oral cancer according to smoking and drinking status

Juliette Rochefort; Ioannis Karagiannidis; Claude Baillou; Lisa Belin; Maude Guillot-Delost; Rodney Macedo; Aline Le Moignic; Véronique Mateo; Patrick Soussan; Isabelle Brocheriou; Jean-Luc Teillaud; Marie-Caroline Dieu-Nosjean; Chloé Bertolus; Francois Michel Lemoine; Géraldine Lescaille

doi:10.3389/fonc.2022.1068979

Defining biomarkers in oral cancer according to smoking and drinking status

Front Oncol. 2023 Jan 11:12:1068979. doi: 10.3389/fonc.2022.1068979. eCollection 2022.

Authors

Juliette Rochefort^{1

2

3}, Ioannis Karagiannidis¹, Claude Baillou¹, Lisa Belin⁴, Maude Guillot-Delost¹, Rodney Macedo¹, Aline Le Moignic¹, Véronique Mateo¹, Patrick Soussan⁵, Isabelle Brocheriou⁶, Jean-Luc Teillaud¹, Marie-Caroline Dieu-Nosjean¹, Chloé Bertolus^{1

7}, Francois Michel Lemoine^{1

8}, Géraldine Lescaille^{1

2

3}

Affiliations

¹ Sorbonne Université, Inserm U.1135, Center of Immunology and Infectious Diseases (Centre d'Immunologie et des Maladies Infectieuses, CIMI-Paris), Paris, France.
² Assistance Publique-Hôpitaux de Paris (AP-HP), Groupe hospitalier Pitié-Salpêtrière, Department of Odontology, Paris, France.
³ Faculty of Odontology Université Paris Cité, Paris, France.
⁴ Sorbonne Université, Inserm, Institut Pierre Louis d'Épidémiologie et de Santé Publique, AP-HP, Hôpitaux Universitaires Pitié-Salpêtrière - Charles Foix, Département de Santé Publique, Paris, France.
⁵ AP-HP, Hôpital Tenon, Department of Virology, Paris, France.
⁶ AP-HP, Groupe hospitalier Pitié-Salpêtrière, Department of Pathology, Paris, France.
⁷ AP-HP, Groupe hospitalier Pitié-Salpêtrière, Department of Maxillo-Facial Surgery, Paris, France.
⁸ AP-HP, Groupe hospitalier Pitié-Salpêtrière, Department of Immunology, Paris, France.

Abstract

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.

Keywords: non-drinker; non-smoker; oral cancer; oral squamous cell carcinoma; prognostic biomarker; tumor microenvironment.

Grants and funding

This work was supported by Institut national du cancer (INCa) (PLBio2016-1-PL BIO-02-ICR-1 grant) (GL, FML), Université Denis Diderot (now Université Paris Cité), Sorbonne Université, AFDS (Association Française pour le Développement de la Stomatologie) (CB), Fondation des Gueules Cassées (JR) and INSERM. JR was supported by a fellowship from the Institut national de la santé et de la recherche médicale (Inserm) and IK by a fellowship from the INCa (PLBio2016-1- PL BIO-02-ICR-1 grant).