Rochefort Juliette, Karagiannidis Ioannis, Baillou Claude, Belin Lisa, Guillot-Delost Maude, Macedo Rodney, Le Moignic Aline, Mateo Véronique, Soussan Patrick, Brocheriou Isabelle, Teillaud Jean-Luc, Dieu-Nosjean Marie-Caroline, Bertolus Chloé, Lemoine Francois Michel, Lescaille Géraldine
Sorbonne Université, Inserm U.1135, Center of Immunology and Infectious Diseases (Centre d'Immunologie et des Maladies Infectieuses, CIMI-Paris), Paris, France.
Assistance Publique-Hôpitaux de Paris (AP-HP), Groupe hospitalier Pitié-Salpêtrière, Department of Odontology, Paris, France.
Front Oncol. 2023 Jan 11;12:1068979. doi: 10.3389/fonc.2022.1068979. eCollection 2022.
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.
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.
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).
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.
口腔鳞状细胞癌（OSCC）大多与吸烟有关，最终与饮酒相关（吸烟/饮酒患者：SD），但25%-30%的患者没有明确的风险因素（非吸烟/非饮酒患者：NSND）。我们假设这些患者具有可区分的免疫特征，这可能对预后有用。
在一项前瞻性病例对照研究中，使用多参数流式细胞术分析了87例OSCC HPV阴性患者免疫肿瘤微环境（TME）中的细胞和血液。通过细胞因子珠阵列（CBA）分析测定肿瘤上清液和血液中的细胞因子水平。
以健康供体（HD）的正常牙龈和血液作为对照。与NSND OSCC患者和HD相比，SD患者的粒细胞（血液中p<0.05）、单核细胞-巨噬细胞（血液中p<0.01）以及表达CD45RO和CCR6的CD4 T细胞（血液中p<0.001；TME中p<0.0001）显著增加，并且IL-6水平更高（血清中p<0.01，肿瘤上清液中p<0.05）。SD OSCC患者肿瘤组织（p=0.05）和血液（p=0.05）中表达CD45RO和CCR6的CD4 T细胞百分比高也与较差的预后相关，而肿瘤组织中高百分比的调节性T细胞（Treg）与更有利的预后因素相关（p=0.05）。此外，NSND患者CD45细胞中血液CD8 T淋巴细胞的百分比更高与无病生存期更好相关（p=0.004）。
因此，血液和TME中的粒细胞、单核细胞-巨噬细胞以及表达CD45RO和CCR6的CD4 T细胞以及血清IL-6可以区分OSCC SD和NSND患者。量化SD患者中表达CD45RO和CCR6的CD4 T细胞以及Treg的比例以及NSND患者中CD8 T细胞的比例可能有助于确定OSCC患者的预后。
