Division of Immunology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital (NKI-AVL), Amsterdam, The Netherlands.
Cancer. 2011 May 15;117(10):2192-201. doi: 10.1002/cncr.25747. Epub 2010 Nov 29.
Cancers are known to elude the immune system, for example, by MHC loss, FAS up-regulation, or increased secretion of TGF-beta. Recently, ligands of coinhibitory receptors like programmed cell death ligand-1 (PD-L1, B7-H1) have come to attention for their role in tumor immune escape. Various tumors have been tested for PD-L1 expression, and conflicting results were obtained regarding its correlative impact on patient survival. This study aimed to determine the prognostic relevance of PD-L1 expression for the survival of melanoma patients.
Paraffin-embedded nevi, primary melanoma, and in-transit, lymph node, and distant organ metastases from a set of 63 stages III-IV melanoma patients referred to the Netherlands Cancer Institute between 2000 and 2004 for a sentinel-node procedure or systemic therapy were studied. A large effort was invested in validating specific PD-L1 staining. In addition to immunological factors such as T-cell infiltration (CD8, CD4, and regulatory T cells), TGF-beta and MHC-I expression were assessed.
Longitudinal analysis revealed no relevant PD-L1 expression on primary melanoma compared with metastatic disease. No significant correlations with prognosis were found regarding immunological factors, whereas known prognostic markers such as Breslow thickness and sex could be confirmed. Analyses of the overall survival of our patient cohort did not reveal a negative association with PD-L1 expression.
Correlation of overall survival with PD-L1 expression by melanoma cells remains controversial, and future clinical studies should focus on antibody validation and time of analysis in respect to disease progression.
众所周知，癌症会逃避免疫系统，例如通过 MHC 丢失、FAS 上调或 TGF-β的过度分泌。最近，共抑制受体的配体（如程序性细胞死亡配体 1（PD-L1，B7-H1））因其在肿瘤免疫逃逸中的作用而受到关注。已经对各种肿瘤进行了 PD-L1 表达测试，但其对患者生存的相关性影响的结果存在争议。本研究旨在确定 PD-L1 表达对黑色素瘤患者生存的预后相关性。
对一组 63 例 III-IV 期黑色素瘤患者的石蜡包埋痣、原发性黑色素瘤以及转移灶（包括局部淋巴结和远处器官转移灶）进行了研究，这些患者于 2000 年至 2004 年期间因前哨淋巴结手术或全身治疗而被转诊至荷兰癌症研究所。我们投入了大量精力来验证 PD-L1 染色的特异性。除了 T 细胞浸润（CD8、CD4 和调节性 T 细胞）等免疫因素外，还评估了 TGF-β和 MHC-I 的表达。
纵向分析显示，原发性黑色素瘤与转移性疾病相比，PD-L1 表达无明显相关性。与预后相关的免疫因素没有发现显著相关性，而 Breslow 厚度和性别等已知的预后标志物可以得到确认。对我们患者队列的总生存分析并未发现与 PD-L1 表达呈负相关。
黑色素瘤细胞的总体生存与 PD-L1 表达的相关性仍存在争议，未来的临床研究应侧重于抗体验证和分析时间与疾病进展的关系。
