Department of Pathology, Fudan University Shanghai Cancer Centre, Shanghai, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Histopathology. 2018 Sep;73(3):386-396. doi: 10.1111/his.13527. Epub 2018 Jun 8.
Programmed cell death protein 1-programmed death-ligand 1 (PD-L1) blockade immunotherapy has shown notable therapeutic benefit in metastatic melanoma, but the clinical relevance of PD-L1 expression remains unclear in melanoma, especially in acral melanoma, which is the most common subtype in Asians. The aim of this study was to evaluate the clinical effect of PD-L1 expression in primary acral melanoma.
We used immunohistochemistry to evaluate PD-L1 expression in tumour cells and tumour-infiltrating lymphocytes (TILs), and analysed its associations with clinicopathological features and survival in 78 primary acral melanoma patients. We found that expression of PD-L1 in tumour cells and TILs occurred exclusively in a tumour-stroma interface pattern, consistent with the predominant pattern of TIL distribution. The presence of peritumoral TILs was also associated with high PD-L1 expression in tumour cells. Furthermore, PD-L1 expression in tumour cells and that in TILs showed a close relationship (Spearman's rho = 0.381, P = 0.001). However, neither PD-L1 expression in tumour cells nor that in TILs was significantly correlated with clinicopathological features. In univariate analysis, cases with PD-L1-positive TILs had significantly poorer survival than those with PD-L1-negative TILs (median disease-specific survival of 40.7 months versus 78.0 months; P = 0.008). In multivariate analysis, PD-L1 expression in TILs was an independent factor for poor prognosis (P = 0.032), whereas PD-L1 expression in tumour cells was not significantly correlated with survival in univariate analysis (P = 0.378) and multivariate analysis (P = 0.354).
This is the first study to demonstrate that PD-L1 expression in TILs, but not that in tumour cells, is an independent predictor of poor prognosis in acral melanoma.
程序性死亡蛋白 1-程序性死亡配体 1（PD-L1）阻断免疫疗法在转移性黑色素瘤中显示出显著的治疗益处，但 PD-L1 表达在黑色素瘤中的临床相关性仍不清楚，尤其是在肢端黑色素瘤中，肢端黑色素瘤是亚洲人中最常见的亚型。本研究旨在评估 PD-L1 表达在原发性肢端黑色素瘤中的临床意义。
我们使用免疫组织化学方法评估了 78 例原发性肢端黑色素瘤患者肿瘤细胞和肿瘤浸润淋巴细胞（TILs）中 PD-L1 的表达，并分析了其与临床病理特征和生存的关系。我们发现，肿瘤细胞和 TILs 中 PD-L1 的表达仅出现在肿瘤-基质界面模式中，与 TIL 分布的主要模式一致。肿瘤周围 TIL 的存在也与肿瘤细胞中高 PD-L1 表达相关。此外，肿瘤细胞中 PD-L1 的表达与 TILs 中 PD-L1 的表达密切相关（Spearman's rho = 0.381，P = 0.001）。然而，肿瘤细胞和 TIL 中 PD-L1 的表达均与临床病理特征无显著相关性。在单因素分析中，PD-L1 阳性 TIL 的病例与 PD-L1 阴性 TIL 的病例相比，生存明显较差（中位疾病特异性生存时间为 40.7 个月与 78.0 个月；P = 0.008）。在多因素分析中，TIL 中 PD-L1 的表达是预后不良的独立因素（P = 0.032），而肿瘤细胞中 PD-L1 的表达在单因素分析（P = 0.378）和多因素分析（P = 0.354）中与生存均无显著相关性。
这是第一项表明 TIL 中 PD-L1 表达而非肿瘤细胞中 PD-L1 表达是肢端黑色素瘤不良预后的独立预测因子的研究。
