PD-L1 stimulation can promote proliferation and survival of leukemic cells by influencing glucose and fatty acid metabolism in acute myeloid leukemia

Soltani, M.; Ghanadian, M.; Ghezelbash, B.; Shokouhi, A.; Zamyatnin, A.A.; Bazhin, A.V.; Ganjalikhani-Hakemi, M.

Авторы: Soltani Mojdeh, Ghanadian Mustafa, Ghezelbash Behrooz, Shokouhi Abolfazl, Zamyatnin Andrey A., Bazhin Alexandr V., Ganjalikhani-Hakemi Mazdak
Журнал: BMC Cancer
Том: 23
Номер: 1
Год издания: 2023
Издательство: BioMed Central
Местоположение издательства: London
Номер статьи: 447
DOI: 10.1186/s12885-023-10947-7
Аннотация: BackgroundLeukemic cell metabolism plays significant roles in their proliferation and survival. These metabolic adaptations are under regulation by different factors. Programmed Death Ligand -1 (CD-274) is one of the immune checkpoint ligands that do not only cause the immune escape of cancer cells, but also have some intracellular effects in these cells. PD-L1 is overexpressed on leukemic stem cells and relates with poor prognosis of AML. In this study, we investigated effects of PD-L1 stimulation on critical metabolic pathways of glucose and fatty acid metabolisms that have important roles in proliferation and survival of leukemic cells.MethodsAfter confirmation of PD-L1 expression by flow cytometry assay, we used recombinant protein PD-1 for stimulation of the PD-L1 on two AML cell lines, HL-60 and THP-1. Then we examined the effect of PD-L1 stimulation on glucose and fatty acid metabolism in cells at the genomic and metabolomic levels in a time dependent manner. We investigated expression changes of rate limiting enzymes of theses metabolic pathways (G6PD, HK-2, CPT1A, ATGL1 and ACC1) by qRT-PCR and also the relative abundance changes of free fatty acids of medium by GC.ResultsWe identified a correlation between PD-L1 stimulation and both fatty acid and glucose metabolism. The PD-L1 stimulated cells showed an influence in the pentose phosphate pathway and glycolysis by increasing expression of G6PD and HK-2 (P value = 0.0001). Furthermore, PD-L1 promoted fatty acid β-oxidation by increasing expression of CPT1A (P value = 0.0001), however, their fatty acid synthesis was decreased by reduction of ACC1 expression (P value = 0.0001).ConclusionWe found that PD-L1 can promote proliferation and survival of AML stem cells probably through some metabolic changes in leukemic cells. Pentose phosphate pathway that has a critical role in cell proliferation and fatty acids β-oxidation that promote cell survival, both are increased by PD-L1 stimulation on AML cells.
Добавил в систему: Замятнин Андрей Александрович

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PD-L1 stimulation can promote proliferation and survival of leukemic cells by influencing glucose and fatty acid metabolism in acute myeloid leukemiaстатья

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