Prognostic value of tumor-infiltrating CD4+ T-cell subpopulations in head and neck cancers
Prognostic value of tumor-infiltrating CD4+ T-cell subpopulations in head and neck cancers
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DOI：
10.1158/1078-0432.ccr-05-1886
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发表时间：
2006-01-15
影响因子：
11.5
通讯作者：
Tartour, E
中科院分区：
文献类型：
--
作者：
Badoual, C;Hans, S;Tartour, E
目的：CD4（+）T细胞在启动和维持抗癌免疫应答中起着重要作用。然而，表达Foxp3的调节性CD4（+）CD25（+）T细胞也显示出抑制抗肿瘤效应T细胞。鉴于这些异质性的CD4（+）T细胞群，本研究旨在确定各种肿瘤浸润的CD4（+）T细胞群在头颈部鳞状细胞癌中的预后价值。实验设计：84例新诊断的未经治疗的经组织学证实的原发性头颈部鳞状细胞癌患者被纳入本研究。进行双重或三重免疫荧光染色以评估和定量活化的CD4（+）CD69（+）T细胞、调节性CD4（+）Foxp3（+）T细胞和包括活化和调节性T细胞的混合的CD4（+）CD25（+）T细胞。在单变量分析中，高水平的肿瘤浸润性CD4（+）CD69（+）T细胞与更好的局部控制（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控制呈正相关。多因素分析显示与局部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）。考克斯多因素分析中，T分期（P = 0.036）和CD4（+）CD69（+）T细胞浸润（P = 0.017）是影响总生存率的两个因素。此外，调节性Foxp3（+）CD4（+）T细胞与局部控制正相关，可能是通过下调有害的炎症反应，这可能有利于肿瘤的进展。
Purpose: 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.Experimental Design: 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.Results: 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).Conclusion: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 downregulation of harmful inflammatory reaction, which could favor tumor progression.