Association Between PD-L1 and HPV Status and the Prognostic Value of PD-L1 in Oropharyngeal Squamous Cell Carcinoma.
Association Between PD-L1 and HPV Status and the Prognostic Value of PD-L1 in Oropharyngeal Squamous Cell Carcinoma.
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PD-L1和HPV状态之间的关联以及PD-L1在口咽鳞癌中的预后价值
DOI：
10.4143/crt.2015.249
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发表时间：
2016-04
影响因子：
4.6
通讯作者：
Ahn MJ
中科院分区：
文献类型：
--
作者：
Kim HS;Lee JY;Lim SH;Park K;Sun JM;Ko YH;Baek CH;Son YI;Jeong HS;Ahn YC;Lee MY;Hong M;Ahn MJ
口咽鳞状细胞癌（OSCC）一直被认为是一种免疫抑制疾病。免疫逃逸的各种机制已经被提出，包括免疫检查点如PD-1:PD-L1通路的失调。我们研究了程序性细胞死亡配体1 （PD-L1）在hpv阴性和hpv阳性OSCC中的表达，以确定其患病率和预后相关性。应用免疫组织化学方法对133例OSCC进行PD-L1表达检测。用PD-L1单克隆抗体（克隆5H1）对福尔马林固定石蜡包埋的肿瘤样品进行染色。PD-L1阳性定义为≥20%的肿瘤细胞膜染色。分析PD-L1表达与HPV状态及生存参数的相关性。133例患者中，68%的患者PD-L1表达，67%的患者免疫组化p16表达阳性。HPV（-）和HPV（+）肿瘤中PD-L1的表达无显著差异（61%对71%，p=0.274）。根据PD-L1状态，年龄、性别、吸烟史、肿瘤起源位置或分期均无显著差异。中位随访时间为44个月，在单因素和多因素分析中，年龄≥65岁（p=0.017）和T3-4期（p<0.001）与总生存期（OS）差相关，而PD-L1表达不影响OS。PD-L1在大多数OSCC患者中均有表达，与HPV状态无关。需要进一步的大型前瞻性研究来确定PD-L1表达作为预后或预测性生物标志物的作用，并且无论HPV状态如何，免疫检查点抑制剂在OCSS中的临床研究都是必要的。
Oropharyngeal squamous cell carcinoma (OSCC) has been recognized as an immunosuppressive disease. Various mechanisms have been proposed for immune escape, including dysregulation of immune checkpoints such as the PD-1:PD-L1 pathway. We investigated the expression of programmed cell death-ligand 1 (PD-L1) in HPV-negative and HPV-positive OSCC to determine its prevalence and prognostic relevance. Using immunohistochemistry, 133 cases of OSCC were evaluated for expression of PD-L1. Formalin-fixed paraffin-embedded tumor samples were stained with monoclonal antibody (clone 5H1) to PD-L1. PD-L1 positivity was defined as membrane staining in ≥20% of tumor cells. Correlations between PD-L1 expression and HPV status and survival parameters were analyzed. Of the 133 patients, 68% showed PD-L1 expression, and 67% of patients were positive for p16 expression by immunohistochemistry. No significant difference in PD-L1 expression was observed between HPV(-) and HPV(+) tumors (61% vs. 71%, p=0.274). No significant difference in age, gender, smoking history, location of tumor origin, or stage was observed according to PD-L1 status. With a median follow-up period of 44 months, older age (≥65) (p=0.017) and T3-4 stage (p<0.001) were associated with poor overall survival (OS), whereas PD-L1 expression did not affect OS in univariate and multivariate analysis. PD-L1 expression was observed in the majority of OSCC patients regardless of HPV status. Further large prospective studies are required to determine the role of PD-L1 expression as a prognostic or predictive biomarker, and clinical studies of immune checkpoint inhibitors in OCSS are warranted regardless of HPV status.