State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan Province, People's Republic of China.
J Immunother. 2021;44(9):339-347. doi: 10.1097/CJI.0000000000000395.
Protein kinase D3 (PKD3) has been involved in various aspects of tumorigenesis and progression in many kinds of cancer types. However, whether PKD3 regulates immune escape in tumor microenvironment is rarely reported. Here, we explored the function and mechanism of PKD3 in reconstructing the immune escape niche of oral squamous cell carcinoma (OSCC). Both the Western blotting analysis in OSCC cells and the gene expression correlation analysis from The Cancer Genome Atlas shows that the expression of Fas and programmed cell death-ligand 1 (PD-L1) was positively correlated with PKD3, while major histocompatibility complex-I (MHC-I) was negatively correlated with PKD3. Knockdown of PKD3 significantly decreased the expression of Fas and PD-L1 and increased the expression of MHC-I. Furthermore, when PKD3 was overexpressed in oral precancerous cells, Fas, PD-L1, and MHC-I showed an opposite trend to that observed when PKD3 was knocked down. In addition, PKD3 knockdown decreased the secretion of transforming growth factor β, CC-chemokine ligand 21, interleukin-10 by OSCC cells. Finally, the tumor cell antigen, which was extracted from PKD3 knockdown OSCC cells, significantly induced the growth and activation of T lymphocytes. These results demonstrate that PKD3 promotes the immune escape of OSCC cells by regulating the expression of Fas, PD-L1, MHC-I, transforming growth factor β, CC-chemokine ligand 21, interleukin-10, and plays a key role in reconstructing the tumor immune escape niche.
蛋白激酶 D3（PKD3）参与了多种癌症类型中肿瘤发生和进展的各个方面。然而，PKD3 是否调节肿瘤微环境中的免疫逃逸很少有报道。在这里，我们研究了 PKD3 在重建口腔鳞状细胞癌（OSCC）免疫逃逸生态位中的功能和机制。OSCC 细胞中的 Western blot 分析和癌症基因组图谱中的基因表达相关性分析表明，Fas 和程序性细胞死亡配体 1（PD-L1）的表达与 PKD3 呈正相关，而主要组织相容性复合体-I（MHC-I）与 PKD3 呈负相关。PKD3 敲低显著降低了 Fas 和 PD-L1 的表达，增加了 MHC-I 的表达。此外，当 PKD3 在口腔癌前细胞中过表达时，Fas、PD-L1 和 MHC-I 的表达趋势与 PKD3 敲低时观察到的相反。此外，PKD3 敲低降低了 OSCC 细胞转化生长因子 β、CC-趋化因子配体 21、白细胞介素-10 的分泌。最后，从 PKD3 敲低的 OSCC 细胞中提取的肿瘤细胞抗原显著诱导了 T 淋巴细胞的生长和激活。这些结果表明，PKD3 通过调节 Fas、PD-L1、MHC-I、转化生长因子 β、CC-趋化因子配体 21、白细胞介素-10 的表达促进 OSCC 细胞的免疫逃逸，在重建肿瘤免疫逃逸生态位中发挥关键作用。
