A comparative view on the expression patterns of PD-L1 and PD-1 in soft tissue sarcomas
A comparative view on the expression patterns of PD-L1 and PD-1 in soft tissue sarcomas
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DOI：
10.1007/s00262-020-02552-5
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发表时间：
2020-03-28
影响因子：
5.8
通讯作者：
Knoesel, Thomas
中科院分区：
文献类型：
--
作者：
Orth, Martin F.;Buecklein, Veit Leonhard;Knoesel, Thomas
软组织肉瘤是一种异质性肿瘤，局部复发和转移率高，预后差。程序性死亡受体配体1(PD-L1)在多种肿瘤中均有表达。PD-L1与其受体PD-1在肿瘤浸润性淋巴细胞(TIL)表面相互作用，从而减弱抗癌免疫反应。针对这种相互作用的免疫检查点抑制剂已被确定为有效的抗癌药物。然而，对PD-L1和PD-1在STS中的表达状态的研究往往受到样本量小、分析单一的STS亚型或缺乏组合标记评估的限制。为了克服这些局限性，我们评估了包括6个STS亚型的225个样本的大型和综合性队列中PD-L1的表达模式、TIL的数量、PD-1的表达及其与临床病理参数的关系。我们发现，几乎所有的STS亚型都在肿瘤细胞上表达PD-L1，尽管在不同亚型中有广泛的阳性表达(50%的血管肉瘤到3%的滑膜肉瘤)。共表达和相关性分析发现，PD-L1的表达与PD-1阳性的TIL(P<；0.001)、较高的肿瘤分级(P=0.016)和较差的患者5年总生存期(P=0.028)相关。这一结果与几篇关于单一STS亚型的文献一致，特别是在比较具有低和高突变负担的STS的结果时。总之，PD-L1阳性的很大一部分，PD-L1阳性TIL的共存，以及PD-L1与不良临床结局的关联，为PD-L1阳性STS患者的免疫检查点抑制提供了理论依据。
Soft tissue sarcomas (STSs) are heterogeneous cancers associated with poor prognosis due to high rates of local recurrence and metastasis. The programmed death receptor ligand 1 (PD-L1) is expressed in several cancers. PD-L1 interacts with its receptor, PD-1, on the surface of tumor-infiltrating lymphocytes (TILs), thereby attenuating anti-cancer immune response. Immune checkpoint inhibitors targeting this interaction have been established as effective anti-cancer drugs. However, studies on the PD-L1 and PD-1 expression status in STS are commonly limited by small sample size, analysis of single STS subtypes, or lack of combinatorial marker assessment. To overcome these limitations, we evaluated the expression patterns of intratumoral PD-L1, the number of TILs, their PD-1 expression, and associations with clinicopathological parameters in a large and comprehensive cohort of 225 samples comprising six STS subtypes. We found that nearly all STS subtypes showed PD-L1 expression on the tumor cells, albeit with a broad range of positivity across subtypes (50% angiosarcomas to 3% synovial sarcomas). Co-expression and correlation analyses uncovered that PD-L1 expression was associated with more PD-1-positive TILs (P < 0.001), higher tumor grading (P = 0.016), and worse patients' 5-year overall survival (P = 0.028). The results were in line with several publications on single STS subtypes, especially when comparing findings for STS with low and high mutational burden. In sum, the substantial portion of PD-L1 positivity, the co-occurrence of PD-1-positive TILs, and the association of PD-L1 with unfavorable clinical outcome provide rationales for immune checkpoint inhibition in patients with PD-L1-positive STS.