In:
Frontiers in Immunology, Frontiers Media SA, Vol. 14 ( 2023-6-12)
Abstract:
Immune therapies targeting the PD-1/PD-L1 pathway have been employed in the treatment of breast cancer, which requires aerobic glycolysis to sustain breast cancer cells growth. However, whether PD-L1 expression is regulated by glycolysis in breast cancer cells remains to be further elucidated. Here, we demonstrate that glycolytic enzyme hexokinase 2 (HK2) plays a crucial role in upregulating PD-L1 expression. Under high glucose conditions, HK2 acts as a protein kinase and phosphorylates IκBα at T291 in breast cancer cells, leading to the rapid degradation of IκBα and activation of NF-κB, which enters the nucleus and promotes PD-L1 expression. Immunohistochemistry staining of human breast cancer specimens and bioinformatics analyses reveals a positive correlation between HK2 and PD-L1 expression levels, which are inversely correlated with immune cell infiltration and survival time of breast cancer patients. These findings uncover the intrinsic and instrumental connection between aerobic glycolysis and PD-L1 expression-mediated tumor cell immune evasion and underscore the potential to target the protein kinase activity of HK2 for breast cancer treatment.
Type of Medium:
Online Resource
ISSN:
1664-3224
DOI:
10.3389/fimmu.2023.1189953
DOI:
10.3389/fimmu.2023.1189953.s001
DOI:
10.3389/fimmu.2023.1189953.s002
Language:
Unknown
Publisher:
Frontiers Media SA
Publication Date:
2023
detail.hit.zdb_id:
2606827-8
