Tumour-infiltrating lymphocytes predict response to definitive chemoradiotherapy in head and neck cancer.
Tumour-infiltrating lymphocytes predict response to definitive chemoradiotherapy in head and neck cancer.
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DOI：
10.1038/bjc.2013.640
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发表时间：
2014-01-21
影响因子：
8.8
通讯作者：
Fokas, E
中科院分区：
文献类型：
--
作者：
Balermpas, P;Michel, Y;Wagenblast, J;Seitz, O;Weiss, C;Rodel, F;Rodel, C;Fokas, E
我们的目的是探讨肿瘤浸润淋巴细胞（TILs）表达的预后价值，在治疗前标本的头颈部鳞状细胞癌（HNSCC）患者接受确定性放化疗（CRT）。采用免疫组织化学方法评估了101例CRT前患者肿瘤组织中CD 3+、CD 8+、CD 4+和FOXP 3 + TIL的患病率，并与临床病理特征以及局部无失败（LFFS）、无远处转移（DMFS）、无进展（PFS）和总生存期（OS）相关。使用Kaplan-Meier方法测量生存曲线，使用对数秩检验估计组间生存差异。使用考克斯回归分析确定TIL亚群密度的预后效应。平均随访25个月（范围：2.3-63个月），整个队列的2年OS为57.4%。免疫组化CD 3和CD 8高表达的患者OS显著增加（P=0.024和P=0.028），PFS（P=0.044和P=0.047）和DMFS（P=0.021和P=0.026）但不是LFFS（P=0.90和P=0.104），包括预测性临床病理因素，如年龄、性别、T分期、N分期、肿瘤分级和定位。CD 4和FOXP 3表达对临床结果均无意义。多因素分析显示，N分期越低，OS越好（P=0.049）。大量浸润性CD 3+和CD 8+细胞与临床结果之间的正相关性表明，TIL可能在HNSCC患者中具有有益作用，并且可以作为生物标志物来识别可能从确定性CRT中受益的患者。
We aimed to investigate the prognostic value of tumour-infiltrating lymphocytes' (TILs) expression in pretreatment specimens from patients with head and neck squamous cell carcinoma (HNSCC) treated with definitive chemoradiotherapy (CRT). The prevalence of CD3+, CD8+, CD4+ and FOXP3+ TILs was assessed using immunohistochemistry in tumour tissue obtained from 101 patients before CRT and was correlated with clinicopathological characteristics as well as local failure-free- (LFFS), distant metastases free- (DMFS), progression-free (PFS) and overall survival (OS). Survival curves were measured using the Kaplan–Meier method, and differences in survival between the groups were estimated using the log-rank test. Prognostic effects of TIL subset density were determined using the Cox regression analysis. With a mean follow-up of 25 months (range, 2.3–63 months), OS at 2 years was 57.4% for the entire cohort. Patients with high immunohistochemical CD3 and CD8 expression had significantly increased OS (P=0.024 and P=0.028), PFS (P=0.044 and P=0.047) and DMFS (P=0.021 and P=0.026) but not LFFS (P=0.90 and P=0.104) in multivariate analysis that included predictive clinicopathologic factors, such as age, sex, T-stage, N-stage, tumour grading and localisation. Neither CD4 nor FOXP3 expression showed significance for the clinical outcome. The lower N-stage was associated with improved OS in the multivariate analysis (P=0.049). The positive correlation between a high number of infiltrating CD3+ and CD8+ cells and clinical outcome indicates that TILs may have a beneficial role in HNSCC patients and may serve as a biomarker to identify patients likely to benefit from definitive CRT.