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首页> 外文期刊>Cellular Physiology and Biochemistry >Membranous and Cytoplasmic Expression of PD-L1 in Ovarian Cancer Cells
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Membranous and Cytoplasmic Expression of PD-L1 in Ovarian Cancer Cells

机译：PD-L1在卵巢癌细胞中的膜和细胞质表达

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>Background: Expression of programmed death-ligand 1 (PD-L1) on tumor cells represents a powerful immune evasion pathway, but the role of intracellular or cytoplasmic PD-L1 has not been investigated in ovarian cancer cells. Methods: Flow cytometry (FCM), Real-time PCR (qPCR), immunohistochemistry (IHC) and western blot were used to determine the expression of PD-L1 in ovarian cancer cells. The cytokines detected in the tumor or tumor associated macrophage (TAM) were used to treat cancer cells. PD-L1 blockade and silencing were used to elucidate the functional significance of cancer-related PD-L1 expression. Results: Based on the results presented, PD-L1 was found variably expressed in the cytoplasm and the cell surface of both HO8910 and SKOV3 cells. TAM or IFN-?3, TNF-?±, IL-10 and IL-6 released from TAM stimulated the expression of PD-L1 at the surface of the cancer cells. The IHC results were consistent with the data in vitro showing infiltration of TAM correlated with membranous PD-L1. The increases of PD-L1 at the surface were not due to a shift in the proportion of surface versus intracellular protein, but the contribution of extracellular signal-regulated kinase (ERK)1/2 and phosphoinositide 3-kinase (PI3K) pathway activation. As a consequence, inducible membranous PD-L1 expression on SKOV3 inhibited CD8+ T cell function, and cytoplasmic PD-L1 promoted cancer cell growth. Additionally, in mouse models, both PD-L1 and PD-1 mAb resulted in tumor growth inhibition and demonstrated a potential to decrease the number of PD-1+CD8+T cells. Conclusion: We conclude that TAM induced PD-L1 on the cancer cells represents an immune evasion mechanism. The observations confirm the therapeutic potential of PD-L1/PD-1 mAb to reactivate anti-tumor immunity in ovarian cancer.
机译：> 背景： 肿瘤细胞上程序性死亡配体1（PD-L1）的表达代表强大的免疫逃逸途径，但在细胞内或细胞质PD- L1尚未在卵巢癌细胞中进行研究。 方法： 使用流式细胞仪（FCM），实时荧光定量PCR（qPCR），免疫组化（IHC）和Western blot检测PD-L1在卵巢癌中的表达细胞。在肿瘤或肿瘤相关巨噬细胞（TAM）中检测到的细胞因子被用于治疗癌细胞。 PD-L1阻断和沉默被用来阐明癌症相关的PD-L1表达的功能意义。 结果： 基于给出的结果，发现PD-L1在HO8910和SKOV3细胞的细胞质和细胞表面中均可变表达。从TAM释放的TAM或IFN-α3，TNF-α，IL-10和IL-6刺激了癌细胞表面PD-L1的表达。 IHC结果与体外数据一致，后者显示TAM与膜性PD-L1相关。表面PD-L1的增加不是由于表面蛋白与细胞内蛋白的比例发生变化，而是由于细胞外信号调节激酶（ERK）1/2和磷酸肌醇3激酶（PI3K）途径活化的作用。结果，SKOV3上可诱导的膜性PD-L1表达抑制了CD8 + T细胞的功能，而胞质PD-L1促进了癌细胞的生长。此外，在小鼠模型中，PD-L1和PD-1 mAb均可抑制肿瘤生长，并显示出减少PD-1 + CD8 + T数量的潜力细胞。 结论： 我们得出的结论是TAM诱导癌细胞上的PD-L1代表免疫逃逸机制。观察结果证实了PD-L1 / PD-1 mAb在卵巢癌中重新激活抗肿瘤免疫力的治疗潜力。

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