Your browser doesn't support javascript.
loading
Glucose-driven histone lactylation promotes the immunosuppressive activity of monocyte-derived macrophages in glioblastoma.
De Leo, Alessandra; Ugolini, Alessio; Yu, Xiaoqing; Scirocchi, Fabio; Scocozza, Delia; Peixoto, Barbara; Pace, Angelica; D'Angelo, Luca; Liu, James K C; Etame, Arnold B; Rughetti, Aurelia; Nuti, Marianna; Santoro, Antonio; Vogelbaum, Michael A; Conejo-Garcia, Jose R; Rodriguez, Paulo C; Veglia, Filippo.
Afiliación
  • De Leo A; Department of Immunology, H. Lee Moffitt Cancer Center, Tampa, FL, USA; Immunology, Microenvironment and Metastasis Program, The Wistar Institute, Philadelphia, PA, USA.
  • Ugolini A; Department of Immunology, H. Lee Moffitt Cancer Center, Tampa, FL, USA; Immunology, Microenvironment and Metastasis Program, The Wistar Institute, Philadelphia, PA, USA; Department of Experimental Medicine "Sapienza" University of Rome, Rome, Italy.
  • Yu X; Department of Biostatistics and Bioinformatic, H. Lee Moffitt Cancer Center, Tampa, FL, USA.
  • Scirocchi F; Department of Immunology, H. Lee Moffitt Cancer Center, Tampa, FL, USA; Department of Experimental Medicine "Sapienza" University of Rome, Rome, Italy.
  • Scocozza D; Department of Immunology, H. Lee Moffitt Cancer Center, Tampa, FL, USA.
  • Peixoto B; Department of Immunology, H. Lee Moffitt Cancer Center, Tampa, FL, USA; Immunology, Microenvironment and Metastasis Program, The Wistar Institute, Philadelphia, PA, USA.
  • Pace A; Department of Experimental Medicine "Sapienza" University of Rome, Rome, Italy.
  • D'Angelo L; Department of Human Neurosciences, Neurosurgery Division, "Sapienza" University, AOU Policlinico Umberto I, Rome, Italy.
  • Liu JKC; Department of Neuro-Oncology, H. Lee Moffitt Cancer Center, Tampa, FL, USA.
  • Etame AB; Department of Neuro-Oncology, H. Lee Moffitt Cancer Center, Tampa, FL, USA.
  • Rughetti A; Department of Experimental Medicine "Sapienza" University of Rome, Rome, Italy.
  • Nuti M; Department of Experimental Medicine "Sapienza" University of Rome, Rome, Italy.
  • Santoro A; Department of Human Neurosciences, Neurosurgery Division, "Sapienza" University, AOU Policlinico Umberto I, Rome, Italy.
  • Vogelbaum MA; Department of Neuro-Oncology, H. Lee Moffitt Cancer Center, Tampa, FL, USA.
  • Conejo-Garcia JR; Department of Integrative immunobiology, Duke School of Medicine, Durham, NC, USA.
  • Rodriguez PC; Department of Immunology, H. Lee Moffitt Cancer Center, Tampa, FL, USA.
  • Veglia F; Department of Immunology, H. Lee Moffitt Cancer Center, Tampa, FL, USA; Department of Neuro-Oncology, H. Lee Moffitt Cancer Center, Tampa, FL, USA; Immunology, Microenvironment and Metastasis Program, The Wistar Institute, Philadelphia, PA, USA. Electronic address: fveglia@wistar.org.
Immunity ; 57(5): 1105-1123.e8, 2024 May 14.
Article en En | MEDLINE | ID: mdl-38703775
ABSTRACT
Immunosuppressive macrophages restrict anti-cancer immunity in glioblastoma (GBM). Here, we studied the contribution of microglia (MGs) and monocyte-derived macrophages (MDMs) to immunosuppression and mechanisms underlying their regulatory function. MDMs outnumbered MGs 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-10 (IL-10) production in MDMs. Inhibition of glycolysis or lactate production in MDMs 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 MDMs was induced downstream of tumor-derived factors that activated the PERK-ATF4 axis. PERK deletion in MDM abrogated histone lactylation, led to the 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.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Histonas / Glioblastoma / Glucosa / Macrófagos Límite: Animals / Humans Idioma: En Revista: Immunity Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Histonas / Glioblastoma / Glucosa / Macrófagos Límite: Animals / Humans Idioma: En Revista: Immunity Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos