Department of Radiation Therapy and Oncology, Johann Wolfgang Goethe University, Frankfurt, Germany.
Senckenberg Institute of Pathology, Johann Wolfgang Goethe University, Frankfurt, Germany.
Br J Cancer. 2014 Jan 21;110(2):501-9. doi: 10.1038/bjc.2013.640. Epub 2013 Oct 15.
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.
本研究旨在探讨头颈部鳞状细胞癌(HNSCC)患者接受根治性放化疗(CRT)前肿瘤浸润淋巴细胞(TILs)表达的预后价值。
采用免疫组织化学方法检测 101 例 CRT 前肿瘤组织中 CD3+、CD8+、CD4+和 FOXP3+TIL 的表达,并与临床病理特征以及局部无失败生存率(LFFS)、远处无转移生存率(DMFS)、无进展生存率(PFS)和总生存率(OS)进行相关性分析。采用 Kaplan-Meier 法绘制生存曲线,对数秩检验比较各组间生存差异。采用 Cox 回归分析 TIL 亚群密度的预后作用。
中位随访时间为 25 个月(范围:2.3-63 个月),全队列 2 年 OS 为 57.4%。高免疫组化 CD3 和 CD8 表达患者的 OS(P=0.024 和 P=0.028)、PFS(P=0.044 和 P=0.047)和 DMFS(P=0.021 和 P=0.026)显著提高,但 LFFS 无显著差异(P=0.90 和 P=0.104),多因素分析纳入预测性临床病理因素,如年龄、性别、T 分期、N 分期、肿瘤分级和肿瘤部位。CD4 和 FOXP3 表达与临床结局无显著相关性。较低的 N 分期与多因素分析中 OS 的改善相关(P=0.049)。
大量浸润性 CD3+和 CD8+细胞与临床结局呈正相关,表明 TILs 可能对头颈部鳞状细胞癌患者具有有益作用,并可作为识别可能从根治性 CRT 中获益的患者的生物标志物。