PDL1 expression is a poor- prognosis factor in soft-tissue sarcomas
PDL1 expression is a poor- prognosis factor in soft-tissue sarcomas
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DOI：
10.1080/2162402x.2016.1278100
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发表时间：
2017-01-01
期刊：
影响因子：
7.2
通讯作者：
Mamessier, Emilie
中科院分区：
文献类型：
--
作者：
Bertucci, Francois;Finetti, Pascal;Mamessier, Emilie
软组织肉瘤(STS)是一组罕见的、异质性和侵袭性的肿瘤，转移风险高，有效的全身治疗相对较少。在寻求新的治疗方法的过程中，免疫系统是一个有吸引力的治疗目标。最近，PD1/PDL1抑制剂在实体瘤患者中显示出非常有希望的结果。PDL1在STS中的表达很少用免疫组织化学方法(IHC)进行研究，仅在小范围内表达，并且与预后不一致。在这里，我们使用DNA微阵列和RNAseq分析了758例临床STS标本中PDL1mRNA的表达，并寻找与包括术后无转移生存(MFS)在内的临床病理变量的相关性。PDL1的表达在样本中是异质性的。PDL1高表达的样本(41%)是更常见的平滑肌肉瘤和脂肪肉瘤，并且更常见地表现出复杂的遗传特征和高风险的CINSARC特征。与肿瘤部位、深度、病理分级、大小等临床病理特征均无相关性。在多变量预后分析中，PDL1高级别与较短的MFS相关，与病理类型和CINSARC信号无关。与生物学因素的相关性分析表明，在PDL1-High类肿瘤中存在强大而有效的细胞毒性T细胞反应，但与一定程度的T细胞耗竭和负调节有关。综上所述，我们认为PDL1的表达改善了手术局部STS中转移复发的预测，而PD1/PDL1的阻断通过重新激活被抑制的T细胞来提高PDL1高表达肿瘤的抗肿瘤免疫，具有改善患者生存的潜力。
Soft-tissue sarcomas (STS) are a group of rare, heterogeneous, and aggressive tumors, with high metastatic risk and relatively few efficient systemic therapies. In the quest for new treatments, the immune system represents an attractive therapeutic target. Recently, PD1/PDL1 inhibitors showed very promising results in patients with solid tumors. PDL1 expression has been rarely studied in STS, in small series only, by using immunohistochemistry (IHC), and with non-concordant prognostic implications. Here, we have analyzed PDL1 mRNA expression in 758 clinical STS samples retrospectively profiled using DNA microarrays and RNAseq, and searched for correlations with clinicopathological variables including metastasis-free survival (MFS) after surgery. PDL1 expression was heterogeneous across the samples. PDL1-high samples (41%) were more frequently leiomyosarcomas and liposarcomas, and showed more frequently a complex genetic profile and a high-risk CINSARC signature. No correlation existed with other clinicopathological features such as tumor site, depth, and pathological tumor grade and size. In multivariate prognostic analysis, the PDL1-high class was associated with shorter MFS, independently of the pathological type and the CINSARC signature. Analysis of correlations with biological factors suggested the existence in tumors of the PDL1-high class of a strong and efficient cytotoxic T-cell response, however associated with some degree of T-cell exhaustion and negative regulation. In conclusion, we show that PDL1 expression refines the prediction of metastatic relapse in operated localized STS, and that PD1/PDL1 blockade holds potential to improve patient survival by reactivating inhibited T cells to increase the antitumor immune in PDL1-high tumors.