| Title : Lysosomal acid lipase, CSF1R and PD-L1 determine functions of CD11c+ myeloid-derived suppressor cells - Zhao_2022_JCI.Insight__ |
| Author(s) : Zhao T , Liu S , Ding X , Johnson EM , Hanna NH , Singh K , Sen CK , Wan J , Du H , Yan C |
| Ref : JCI Insight , : , 2022 |
| Abstract : Lysosomal acid lipase (LAL) is a key enzyme in the metabolic pathway of neutral lipids. In the blood of LAL deficient (lal-/-) mice, increased CD11c+ cells were accompanied by up-regulated PD-L1 expression. Single cell RNA sequencing of lal-/- CD11c+ cells identified two distinctive clusters with a major metabolic shift towards glucose utilization and reactive oxygen species (ROS) over-production. Pharmacologically blocking pyruvate dehydrogenase in glycolysis not only reduced CD11c+ cells and their PD-L1 expression, but also reversed their capabilities of T cell suppression and tumor growth stimulation. Colony-stimulating factor 1 receptor (CSF1R) plays an essential role in controlling lal-/- CD11c+ cell homeostasis and function and PD-L1 expression. Inhibition of LAL activity by pharmacological inhibitor increased CD11c, PD-L1 and CSF1R levels in both normal murine myeloid cells and human blood cells. Tumor-bearing mice and human non-small-cell lung cancer (NSCLC) patients also showed CD11c+ cell expansion with PD-L1 and CSF1R up-regulation and immunosuppression. There were positive correlations among CD11c, PD-L1 and CSF1R expression and negative correlations with LAL expression in lung cancer and melanoma patients using the TCGA database and patient samples. Therefore, CD11c+ cells switched their functions to immune suppression and tumor growth stimulation through CSF1R/PD-L1 upregulation and metabolic reprogramming. |
| ESTHER : Zhao_2022_JCI.Insight__ |
| PubMedSearch : Zhao_2022_JCI.Insight__ |
| PubMedID: 35917184 |
Zhao T, Liu S, Ding X, Johnson EM, Hanna NH, Singh K, Sen CK, Wan J, Du H, Yan C (2022)
Lysosomal acid lipase, CSF1R and PD-L1 determine functions of CD11c+ myeloid-derived suppressor cells
JCI Insight
:
Zhao T, Liu S, Ding X, Johnson EM, Hanna NH, Singh K, Sen CK, Wan J, Du H, Yan C (2022)
JCI Insight
: