The DOI matches its Crossref record; 85 of the 85 references it cites were found in a registry or an index.
Glucose-driven histone lactylation promotes the immunosuppressive activity of monocyte-derived macrophages in glioblastoma
Open accessAbstract
Summary Immunosuppressive macrophages restrict anti-cancer immunity in glioblastoma (GBM). Here, we studied the contribution of microglia (MG) and monocyte-derived macrophages (MDM) to immunosuppression, and mechanisms underlying their regulatory function. MDM outnumbered MG at late tumor stages and suppressed T cell activity. Molecular and functional analysis identified a population of glycolytic MDM expressing GLUT1 with potent immunosuppressive activity. GBM-derived factors promoted high glycolysis, lactate and interleukin-(IL)10 production in MDM. Inhibition of glycolysis or lactate production in MDM impaired IL-10 expression and T cell suppression. Mechanistically, intracellular lactate-driven histone lactylation promoted IL-10 expression, which was required to suppress T cell activity. GLUT1 expression on MDM was induced downstream of tumor-derived factors that activated the PERK-ATF4 axis. PERK deletion in MDM abrogated histone lactylation, led to accumulation of intratumoral T cells and tumor growth delay, and in combination with immunotherapy, blocked GBM progression. Thus, PERK-driven glucose metabolism promotes MDM immunosuppressive activity via histone lactylation.
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Metadata
- Authors
- De Leo, A., Ugolini, A., Yu, X., Scirocchi, F., Scocozza, D., Peixoto, B., Pace, A., D’Angelo, L., Liu, J. K. C., Etame, A. B., Rughetti, A., Nuti, M., Santoro, A., Vogelbaum, M. A., Conejo-Garcia, J. R., Rodriguez, P. C., & Veglia, F.
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2024-05
- Volume
- 57
- Issue
- 5
- Pages
- 1105-1123.e8
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W4396610782
- Cited by
- 319
- References
- 85
- FWCI
- 43.60
- Type
- journal article
- Language
- en
- Open access
- bronze
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- De Leo, A., Ugolini, A., Yu, X., Scirocchi, F., Scocozza, D., Peixoto, B., Pace, A., D’Angelo, L., Liu, J. K. C., Etame, A. B., Rughetti, A., Nuti, M., Santoro, A., Vogelbaum, M. A., Conejo-Garcia, J. R., Rodriguez, P. C., & Veglia, F. (2024). Glucose-driven histone lactylation promotes the immunosuppressive activity of monocyte-derived macrophages in glioblastoma. Immunity. https://doi.org/10.1016/j.immuni.2024.04.006
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