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.
Original language | English (US) |
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Pages (from-to) | 42414-42427 |
Number of pages | 14 |
Journal | Oncotarget |
Volume | 8 |
Issue number | 26 |
DOIs | |
State | Published - 2017 |
Keywords
- AKT
- NF-κB
- PD-L1
- PIPKIγ
- Triple negative breast cancer
ASJC Scopus subject areas
- Oncology