Badoual Cécile, Hans Stéphane, Rodriguez José, Peyrard Severine, Klein Christophe, Agueznay Nour El Houda, Mosseri Véronique, Laccourreye Ollivier, Bruneval Patrick, Fridman Wolf H, Brasnu Daniel F, Tartour Eric
Institut National de la Sante et de la Recherche Medicale U255, IFR58, Institut Biomedical des Cordeliers, Université Paris 5, Paris, France.
Clin Cancer Res. 2006 Jan 15;12(2):465-72. doi: 10.1158/1078-0432.CCR-05-1886.
CD4(+) T cells play a central role in initiating and maintaining anticancer immune responses. However, regulatory CD4(+)CD25(+) T cells which express Foxp3 have also been shown to inhibit antitumor effector T cells. In view of these heterogeneous CD4(+) T-cell populations, this study was designed to determine the prognostic value of various tumor-infiltrating CD4(+) T-cell populations in head and neck squamous cell carcinoma.
Eighty-four newly diagnosed untreated patients with histologically proven primary head and neck squamous cell carcinoma were included in this study. Double or triple immunofluorescence staining was done to assess and quantify the activated CD4(+)CD69(+) T cells, regulatory CD4(+)Foxp3(+) T cells, and mixed CD4(+)CD25(+) T cells comprising both activated and regulatory T cells.
On univariate analysis, high levels of tumor-infiltrating CD4(+)CD69(+) T cells were correlated with both better locoregional control (P = 0.01) and longer survival (P = 0.01). Infiltration by regulatory Foxp3(+)CD4(+) T cells was positively associated with a better locoregional control of the tumor. Multivariate analysis showed that the only significant prognostic factors related to locoregional control were T stage (P = 0.02) and CD4(+)Foxp3(+) T-cell infiltration of the tumor (P = 0.02). In the Cox multivariate analysis, only two variables influenced overall survival probability: T stage (P = 0.036) and CD4(+)CD69(+) T-cell infiltration (P = 0.017).
This study shows that tumor-infiltrating activated CD4(+)CD69(+) T cells are associated with a good prognosis in head and neck squamous cell carcinoma. In addition, regulatory Foxp3(+)CD4(+) T cells are positively correlated with locoregional control may be through down-regulation of harmful inflammatory reaction, which could favor tumor progression.
CD4(+) T细胞在启动和维持抗癌免疫反应中起核心作用。然而，表达Foxp3的调节性CD4(+)CD25(+) T细胞也已被证明可抑制抗肿瘤效应T细胞。鉴于这些异质性CD4(+) T细胞群体，本研究旨在确定各种肿瘤浸润性CD4(+) T细胞群体在头颈部鳞状细胞癌中的预后价值。
本研究纳入了84例新诊断的未经治疗且经组织学证实为原发性头颈部鳞状细胞癌的患者。进行双重或三重免疫荧光染色以评估和量化活化的CD4(+)CD69(+) T细胞、调节性CD4(+)Foxp3(+) T细胞以及包含活化和调节性T细胞的混合CD4(+)CD25(+) T细胞。
单因素分析显示，高水平的肿瘤浸润性CD4(+)CD69(+) T细胞与更好的局部区域控制（P = 0.01）和更长的生存期（P = 0.01）相关。调节性Foxp3(+)CD4(+) T细胞的浸润与肿瘤更好的局部区域控制呈正相关。多因素分析表明，与局部区域控制相关的唯一显著预后因素是T分期（P = 0.02）和肿瘤的CD4(+)Foxp3(+) T细胞浸润（P = 0.02）。在Cox多因素分析中，仅两个变量影响总生存概率：T分期（P = 0.036）和CD4(+)CD69(+) T细胞浸润（P = 0.017）。
本研究表明，肿瘤浸润性活化CD4(+)CD69(+) T细胞与头颈部鳞状细胞癌的良好预后相关。此外，调节性Foxp3(+)CD4(+) T细胞与局部区域控制呈正相关，可能是通过下调有害的炎症反应，这可能有利于肿瘤进展。
