CD8+tumour-infiltrating lymphocytes in relation to HPV status and clinical outcome in patients with head and neck cancer after postoperative chemoradiotherapy: A multicentre study of the German cancer consortium radiation oncology group (DKTK-ROG)
CD8+tumour-infiltrating lymphocytes in relation to HPV status and clinical outcome in patients with head and neck cancer after postoperative chemoradiotherapy: A multicentre study of the German cancer consortium radiation oncology group (DKTK-ROG)
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DOI：
10.1002/ijc.29683
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发表时间：
2016-01-01
影响因子：
6.4
通讯作者：
Fokas, Emmanouil
中科院分区：
文献类型：
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作者：
Balermpas, Panagiotis;Roedel, Franz;Fokas, Emmanouil
我们研究了头颈部鳞状细胞癌(SCCHN)患者术后肿瘤浸润性淋巴细胞(TIL)和术后以顺铂为基础的放化疗的预后价值。取自8个DKTK配对部位的161例患者手术切除的FFPE组织进行CD3和CD8免疫组织化学染色。HPV16-DNA/p16表达与临床病理特征、总生存期(OS)、无局部进展生存期(LPFS)和无远处转移生存期(DMFS)相关。经过48个月(范围：4100个月)的中位随访，4年的OS在整个队列中为46.5%。在多因素分析中，CD8的高表达是OS(p=0.002)、LPFS(p=0.004)和DMFS(p=0.006)的独立预后参数，而CD3的表达缺乏统计学意义。在多变量分析中，HPV16DNA阳性与OS(p=0.025)和LPFS(p=0.013)的改善有关，而p16阳性患者的DMFS(p=0.008)改善。有趣的是，在HPV16DNA阳性和HPV16DNA阴性的患者中，CD8的高表达都是一个预测临床结果的参数。在对HPV16DNA/p16联合状态的多变量分析中也观察到了类似的发现。总之，CD8+TIL是接受辅助化放疗治疗的SCCHN患者的独立预后标志物。这些数据表明CD8阳性的TIL具有抗肿瘤活性，可用于治疗分层。进一步验证CD8+TIL作为生物标志物的预后价值及其在SCCHN患者辅助放化疗后免疫反应中的作用是有必要的，并将在未来的DKTK-ROG研究中进行。有什么新消息？头颈部鳞状细胞癌(SCCHN)不是一组同质的肿瘤。这意味着迫切需要生物标记物，以便使预后和治疗能够个体化。在这项研究中，作者发现，肿瘤内CD8+肿瘤浸润性淋巴细胞(TIL)水平较高的患者在治疗后结果有所改善。这些结果提示CD8阳性的TIL可能具有抗肿瘤活性，它们的表达可能是治疗分层的有用的预后生物标志物。头颈部鳞状细胞癌(SCCHN)约占癌症总发病率的6%，全球每年约有50万新确诊病例。局部晚期SCCHN一般采用根治性手术，包括肿瘤切除、区域淋巴结清扫、术后放化疗(CRT)，5年生存率为40-60%。
We examined the prognostic value of tumour-infiltrating lymphocytes (TILs) in patients with squamous cell carcinoma of the head and neck (SCCHN) after surgery and postoperative cisplatin-based chemoradiotherapy. FFPE-tissue originating from the surgery of 161 patients treated in 8 DKTK partner sites was immunohistochemically stained for CD3 and CD8. Their expression was correlated with clinicopathological characteristics as well as overall survival (OS), local progression-free survival (LPFS) and distant metastases free-survival (DMFS), also in the context of the HPV16-DNA/p16 status. After a median follow-up of 48 months (range: 4100 months), OS at 4 years was 46.5% for the entire cohort. In multivariate analysis, high CD8 expression was confirmed as an independent prognostic parameter for OS (p=0.002), LPFS (p=0.004) and DMFS (p=0.006), while CD3 expression lacked significance. In multivariate analysis HPV16 DNA positivity was associated with improved OS (p=0.025) and LPFS (p=0.013) and p16-positive patients showed improved DMFS (p=0.008). Interestingly, high CD8 expression was a prognostic parameter for the clinical outcome in both HPV16 DNA-positive and HPV16 DNA-negative patients. Similar findings were observed in the multivariate analysis for the combined HPV16 DNA/p16 status. Altogether, CD8+ TILs constitute an independent prognostic marker in SCCHN patients treated with adjuvant chemoradiotherapy. These data indicate that CD8-positive TILs have antitumour activity and could be used for treatment stratification. Further validation of the prognostic value of CD8+ TILs as a biomarker and its role in the immune response in SCCHN patients after adjuvant chemoradiotherapy is warranted and will be performed in the prospective DKTK-ROG study.What's New? Squamous cell carcinomas of the head and neck (SCCHN) are not a homogenous group of tumors. This means that biomarkers are urgently needed, so that prognosis and treatment can be individualised. In this study, the authors found that patients with higher levels of CD8+ tumor-infiltrating lymphocytes (TILs) within their tumors had improved outcomes after treatment. These results suggest that CD8-positive TILs may have antitumor activity, and that their expression may be a useful prognostic biomarker for treatment stratification. Squamous cell carcinoma of the head and neck (SCCHN) represents about 6% of the total cancer incidence and approximately 500,000 new cases are diagnosed each year worldwide. Radical surgery including resection of the primary tumour and neck dissection of regional lymph nodes followed by postoperative chemoradiotherapy (CRT) is commonly performed in locally advanced SCCHN with a 5-year survival rate of 40-60% .