Type Iγ phosphatidylinositol phosphate kinase regulates PD-L1 expression by activating NF-κB.

Abstract

The programmed death-ligand 1 (PD-L1), by binding to PD-1 on the surface of immune cells, activates a major immune checkpoint pathway. Elevated expression of PD-L1 in tumor cells mediates tumor-induced T-cell exhaustion and immune suppression; therefore protect the survival of tumor cells. Although blockade of the PD-1/PD-L1 axis exhibits great potential in cancer treatment, mechanisms driving the up-regulation of PD-L1 in tumor cells remain not fully understood. Here we found that type Iγ phosphatidylinositol 4-phosphate (PtdIns(4)P) 5-kinase (PIPKIγ) is required for PD-L1 expression in triple negative breast cancer cells. Depletion of PIPKIγ inhibits both intrinsic and induced PD-L1 expression. Results from further analyses suggest that PIPKIγ promotes the transcription of the PD-L1 gene by activating the NF-κB pathway in these cells. These results demonstrate that PIPKIγ-dependent expression of PD-L1 is likely important for the progression of triple negative breast cancer.

• Authors: Junli Xue, Chunhua Chen, Manlong Qi, Yan Huang, Lin Wang, Yong Gao, Haidong Dong, Kun Ling
• Journal: Oncotarget (Oncotarget) Vol. 8 Issue 26 Pg. 42414-42427 (Jun 27 2017) ISSN: 1949-2553 [Electronic] United States
• PMID: 28465490 (Publication Type: Journal Article)

Chemical References

• B7-H1 Antigen
• CD274 protein, human
• NF-kappa B
• Phosphotransferases (Alcohol Group Acceptor)
• 1-phosphatidylinositol-4-phosphate 5-kinase

Topics

• B7-H1 Antigen (genetics)
• Cell Line, Tumor
• Disease Progression
• Enzyme Activation
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• NF-kappa B (agonists, metabolism)
• Phosphorylation
• Phosphotransferases (Alcohol Group Acceptor) (genetics, metabolism)
• Signal Transduction
• Transcription, Genetic
• Triple Negative Breast Neoplasms (genetics, metabolism, pathology)