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肿瘤浸润淋巴细胞预测头颈部癌症患者接受根治性放化疗的反应。

Tumour-infiltrating lymphocytes predict response to definitive chemoradiotherapy in head and neck cancer.

机构信息

Department of Radiation Therapy and Oncology, Johann Wolfgang Goethe University, Frankfurt, Germany.

Senckenberg Institute of Pathology, Johann Wolfgang Goethe University, Frankfurt, Germany.

出版信息

Br J Cancer. 2014 Jan 21;110(2):501-9. doi: 10.1038/bjc.2013.640. Epub 2013 Oct 15.

Abstract

BACKGROUND

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).

METHODS

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.

RESULTS

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).

CONCLUSION

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.

摘要

背景

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。

方法

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。

结果

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)。

结论

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。

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