PD-1/PD-L1 表达在葡萄膜黑色素瘤中的预后意义：与肿瘤浸润淋巴细胞和临床病理参数的相关性。
Prognostic significance of PD-1/PD-L1 expression in uveal melanoma: correlation with tumor-infiltrating lymphocytes and clinicopathological parameters.
机构信息
Department of Ocular Pathology, Dr. R P. Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India.
Department of Ophthalmology, Gavin Herbert Eye Institute, University of California, Irvine, USA.
出版信息
Cancer Immunol Immunother. 2021 May;70(5):1291-1303. doi: 10.1007/s00262-020-02773-8. Epub 2020 Nov 2.
BACKGROUND
To understand how to improve the effect of immune checkpoint inhibitors in uveal melanoma (UM), we need a better understanding of the expression of PD-1 and PD-L1, their relation with the presence of tumor-infiltrating lymphocytes (TILs), and their prognostic relevance in UM patients.
MATERIALS AND METHODS
Expression of PD-1 and PD-L1 was assessed in 71 UM tissue samples by immunohistochemistry and quantitative real-time PCR (qRT-PCR), and further validated by western blotting. The effect of interferon gamma (IFN-γ) on PD-1/PD-L1 expression was determined on four UM cell lines.
RESULTS
Immunoreactivity of PD-1 was found in 30/71 cases and of PD-L1 in 44/71 UM samples. Tumor-infiltrating lymphocytes were found in 46% of UM tissues. PD-1 was expressed on TILs while tumor cells expressed PD-L1. UM with and without TILs showed expression of PD-1 in 69% and 18% cases, respectively (p = 0.001). Similarly, PD-L1 was found in 75% of UM with TILs and in 50% of cases without TILs, respectively (p = 0.03). DFS rate were lower in patients with TILs with expression of PD-1 and PD-L1, but the rate of DFS was higher with expression of PD-L1 in patients without TILs. After treatment of UM cell lines with IFN-γ, PD-1 expression was induced in all UM cell lines whereas PD-L1 expression was found at a lower level in untreated cells, while expression also increased following treatment with IFN-γ.
CONCLUSION
Our study suggests that increased infiltration with TILs promotes the aggressive behavior and suppresses the immune response of UM cells, thereby inhibiting immunotherapy.
背景
为了了解如何提高免疫检查点抑制剂在葡萄膜黑色素瘤（UM）中的疗效，我们需要更好地了解 PD-1 和 PD-L1 的表达、它们与肿瘤浸润淋巴细胞（TILs）的存在的关系，以及它们在 UM 患者中的预后相关性。
材料和方法
通过免疫组织化学和实时定量 PCR（qRT-PCR）评估了 71 例 UM 组织样本中 PD-1 和 PD-L1 的表达，并通过 Western blot 进一步验证。测定干扰素γ（IFN-γ）对四种 UM 细胞系中 PD-1/PD-L1 表达的影响。
结果
在 71 例 UM 样本中，有 30 例检测到 PD-1 免疫反应性，44 例检测到 PD-L1 免疫反应性。在 46%的 UM 组织中发现了肿瘤浸润淋巴细胞。TILs 表达 PD-1，而肿瘤细胞表达 PD-L1。有和没有 TILs 的 UM 分别有 69%和 18%的病例表达 PD-1（p=0.001）。同样，有 TILs 的 UM 中有 75%和没有 TILs 的 UM 中有 50%分别发现 PD-L1 的表达（p=0.03）。在有 TILs 表达 PD-1 和 PD-L1 的患者中，DFS 率较低，但在没有 TILs 表达 PD-L1 的患者中，DFS 率较高。用 IFN-γ处理 UM 细胞系后，所有 UM 细胞系中均诱导表达 PD-1，而未经处理的细胞中 PD-L1 表达水平较低，用 IFN-γ处理后表达也增加。
结论
我们的研究表明，TILs 的浸润增加促进了 UM 细胞的侵袭行为并抑制了免疫反应，从而抑制了免疫治疗。
Zotero 插件