The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.
Aerobic glycolysis promotes tumor immune evasion by hexokinase2-mediated phosphorylation of IκBα
Open accessAbstract
High expression of PD-L1 in tumor cells contributes to tumor immune evasion. However, whether PD-L1 expression in tumor cells is regulated by the availability of nutrients is unknown. Here, we show that in human glioblastoma cells, high glucose promotes hexokinase (HK) 2 dissociation from mitochondria and its subsequent binding and phosphorylation of IκBα at T291. This leads to increased interaction between IκBα and μ-calpain protease and subsequent μ-calpain-mediated IκBα degradation and NF-κB activation-dependent transcriptional upregulation of PD-L1 expression. Expression of IκBα T291A in glioblastoma cells blocked high glucose-induced PD-L1 expression and promoted CD8+ T cell activation and infiltration into the tumor tissue, reducing brain tumor growth. Combined treatment with an HK inhibitor and an anti-PD-1 antibody eliminates tumor immune evasion and remarkably enhances the anti-tumor effect of immune checkpoint blockade. These findings elucidate a novel mechanism underlying the upregulation of PD-L1 expression mediated by aerobic glycolysis and underscore the roles of HK2 as a glucose sensor and a protein kinase in regulation of tumor immune evasion.
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Cited by
Zhong, Q., Xiao, X., Qiu, Y., Xu, Z., Chen, C., Chong, B., Zhao, X., Hai, S., Li, S., An, Z., et al. (2023) · MedComm · doi:10.1002/mco2.261 · Cited by 442
Self-citationDecoding microglial immunometabolism: a new frontier in Alzheimer's disease research
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Zhao, J., Jin, D., Huang, M., Ji, J., Xu, X., Wang, F., Zhou, L., Bao, B., Jiang, F., Xu, W., et al. (2024) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2024.1416472 · Cited by 84
Codocedo, J. F., Mera-Reina, C., Bor-Chian Lin, P., Fallen, P. B., Puntambekar, S. S., Casali, B. T., Jury-Garfe, N., Martinez, P., Lasagna-Reeves, C. A., & Landreth, G. E. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.114488 · Cited by 52
Imaging glucose metabolism to reveal tumor progression
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Metadata
- Authors
- Guo, D., Tong, Y., Jiang, X., Meng, Y., Jiang, H., Du, L., Wu, Q., Li, S., Luo, S., Li, M., Xiao, L., He, H., He, X., Yu, Q., Fang, J., & Lu, Z.
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2022-09
- Volume
- 34
- Issue
- 9
- Pages
- 1312-1324.e6
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W4292951314
- Cited by
- 423
- References
- 43
- FWCI
- 27.70
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Guo, D., Tong, Y., Jiang, X., Meng, Y., Jiang, H., Du, L., Wu, Q., Li, S., Luo, S., Li, M., Xiao, L., He, H., He, X., Yu, Q., Fang, J., & Lu, Z. (2022). Aerobic glycolysis promotes tumor immune evasion by hexokinase2-mediated phosphorylation of IκBα. Cell Metabolism. https://doi.org/10.1016/j.cmet.2022.08.002
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