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肿瘤浸润淋巴细胞中的 PD-L1 表达是原发性肢端黑色素瘤患者的预后不良因素。

PD-L1 expression in tumour-infiltrating lymphocytes is a poor prognostic factor for primary acral melanoma patients.

机构信息

Department of Pathology, Fudan University Shanghai Cancer Centre, Shanghai, China.

Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.

出版信息

Histopathology. 2018 Sep;73(3):386-396. doi: 10.1111/his.13527. Epub 2018 Jun 8.

Abstract

AIMS

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.

METHODS AND RESULTS

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).

CONCLUSION

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.

摘要

目的

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。

方法和结果

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。

结论

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。

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