Differential modulation and prognostic values of immune-escape genes in uveal melanoma
Differential modulation and prognostic values of immune-escape genes in uveal melanoma
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DOI：
10.1371/journal.pone.0210276
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发表时间：
2019-01-17
期刊：
影响因子：
3.7
通讯作者：
Reibaldi, Michele
中科院分区：
文献类型：
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作者：
Basile, Maria Sofia;Mazzon, Emanuela;Reibaldi, Michele
葡萄膜黑色素瘤（UM）是成人最常见的原发性眼内癌。在本研究中，我们旨在描述原发性UM癌的免疫学特征，并提供与预后标志物和结果的关联。此外，我们评估了微环境对UM中抑制性免疫检查点表达的影响。感兴趣的基因包括MHC I类和II类分子，以及抑制免疫检查点，即PDL1、PDL2、B7-H3、B7-H4、TBFRSF6B、CD47、CD155、GAL9、HVEM和CD200。我们观察到与正常葡萄膜黑色素细胞相比，UM细胞中的MHC基因水平显著降低。然而，出乎意料的是，除了CD200和HVEM外，大多数被分析的抑制免疫检查点基因的表达水平在癌细胞中与正常黑色素细胞相比没有差异，导致显著降低。另一方面，PDL1与OS、PFS和肿瘤厚度呈负相关。此外，在炎症条件下，PDL1和PDL2的表达显著增加。最后，我们首次提出了CD47在UM免疫逃避特性中的可能作用。我们在这里表明CD47在炎症刺激后被UM细胞显著上调，并且它代表了疾病进展的一个很好的独立预测因子。这项研究的结果可能会推动UM患者免疫治疗的发展。
Uveal melanoma (UM) is the most common primary intraocular cancer in adults. In the present study, we aimed to characterize the immunological features of primary UM cancer and to provide an association with prognostic markers and outcome. Also, we assessed the influence of the microenvironment on the expression of inhibitory immune checkpoints in UM. Genes of interest included MHC Class I and Class II molecules, as well as inhibitory immune-checkpoints, i.e. PDL1, PDL2, B7-H3, B7-H4, TBFRSF6B, CD47, CD155, GAL9, HVEM and CD200. We observed significant lower levels of MHC genes in UM cells as compared to normal uveal melanocytes. Unexpectedly however, the expression levels of most of the analyzed inhibitory immune-checkpoint genes were not different in cancer cells as compared to normal melanocytes, with the exception of CD200 and HVEM, that resulted significantly reduced. On the other hand, PDL1 inversely correlated with OS, PFS and thickness of the tumor. Also, PDL1, along with PDL2, expression significantly increased under inflammatory conditions. Finally, for the first time, we propose a possible role for CD47 in the immune evasive properties of UM. We show here that CD47 is significantly upregulated by UM cells following inflammatory stimuli and that it represents a good independent predictor of disease progression. The results from this study may propel advances in the development of immune-based therapies for UM patients.