Protein Kinase D3 Promotes the Reconstruction of OSCC Immune Escape Niche Via Regulating MHC-I and Immune Inhibit Molecules Expression.

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 beta, 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 beta, CC-chemokine ligand 21, interleukin-10, and plays a key role in reconstructing the tumor immune escape niche.