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) |
|---|---|
| Pages (from-to) | 42414-42427 |
| Number of pages | 14 |
| Journal | Oncotarget |
| Volume | 8 |
| Issue number | 26 |
| DOIs | |
| State | Published - 2017 |
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Keywords
- AKT
- NF-κB
- PD-L1
- PIPKIγ
- Triple negative breast cancer
ASJC Scopus subject areas
- Oncology
Cite this
Type Iγ phosphatidylinositol phosphate kinase regulates PD-L1 expression by activating NF-κB. / Xue, Junli; Chen, Chunhua; Qi, Manlong; Huang, Yan; Wang, Lin; Gao, Yong; Dong, Haidong M; Ling, Kun.
In: Oncotarget, Vol. 8, No. 26, 2017, p. 42414-42427.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Type Iγ phosphatidylinositol phosphate kinase regulates PD-L1 expression by activating NF-κB
AU - Xue, Junli
AU - Chen, Chunhua
AU - Qi, Manlong
AU - Huang, Yan
AU - Wang, Lin
AU - Gao, Yong
AU - Dong, Haidong M
AU - Ling, Kun
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
KW - AKT
KW - NF-κB
KW - PD-L1
KW - PIPKIγ
KW - Triple negative breast cancer
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U2 - 10.18632/oncotarget.17123
DO - 10.18632/oncotarget.17123
M3 - Article
VL - 8
SP - 42414
EP - 42427
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 26
ER -