Your browser doesn't support javascript.
loading
The immunosuppression pathway of tumor-associated macrophages is controlled by heme oxygenase-1 in glioblastoma patients.
Magri, Sara; Musca, Beatrice; Pinton, Laura; Orecchini, Elena; Belladonna, Maria Laura; Orabona, Ciriana; Bonaudo, Camilla; Volpin, Francesco; Ciccarino, Pietro; Baro, Valentina; Della Puppa, Alessandro; Mandruzzato, Susanna.
Afiliación
  • Magri S; Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy.
  • Musca B; Immunology and Molecular Oncology, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy.
  • Pinton L; Immunology and Molecular Oncology, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy.
  • Orecchini E; Department of Medicine and Surgery, University of Perugia, Perugia, Italy.
  • Belladonna ML; Department of Medicine and Surgery, University of Perugia, Perugia, Italy.
  • Orabona C; Department of Medicine and Surgery, University of Perugia, Perugia, Italy.
  • Bonaudo C; Neurosurgery, Department of NEUROFARBA, University of Florence, University Hospital of Careggi, Florence, Italy.
  • Volpin F; Neurosurgery Department, University Hospital of Padova, Padova, Italy.
  • Ciccarino P; Neurosurgery Department, University Hospital of Padova, Padova, Italy.
  • Baro V; Academic Neurosurgery, Department of Neurosciences, University of Padova, Padova, Italy.
  • Della Puppa A; Neurosurgery, Department of NEUROFARBA, University of Florence, University Hospital of Careggi, Florence, Italy.
  • Mandruzzato S; Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy.
Int J Cancer ; 151(12): 2265-2277, 2022 Dec 15.
Article en En | MEDLINE | ID: mdl-36054818
The immunosuppressive tumor microenvironment (TME) in glioblastoma (GBM) is mainly driven by tumor-associated macrophages (TAMs). We explored whether their sustained iron metabolism and immunosuppressive activity were correlated, and whether blocking the central enzyme of the heme catabolism pathway, heme oxygenase-1 (HO-1), could reverse their tolerogenic activity. To this end, we investigated iron metabolism in bone marrow-derived macrophages (BMDMs) isolated from GBM specimens and in in vitro-derived macrophages (Mφ) from healthy donor (HD) blood monocytes. We found that HO-1 inhibition abrogated the immunosuppressive activity of both BMDMs and Mφ, and that immunosuppression requires both cell-to-cell contact and soluble factors, as HO-1 inhibition abolished IL-10 release, and significantly reduced STAT3 activation as well as PD-L1 expression. Interestingly, not only did HO-1 inhibition downregulate IDO1 and ARG-2 gene expression, but also reduced IDO1 enzymatic activity. Moreover, T cell activation status affected PD-L1 expression and IDO1 activity, which were upregulated in the presence of activated, but not resting, T cells. Our results highlight the crucial role of HO-1 in the immunosuppressive activity of macrophages in the GBM TME and demonstrate the feasibility of reprogramming them as an alternative therapeutic strategy for restoring immune surveillance.
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: Glioblastoma / Hemo-Oxigenasa 1 / Macrófagos Asociados a Tumores Tipo de estudio: Risk_factors_studies Límite: Humans Idioma: En Revista: Int J Cancer Año: 2022 Tipo del documento: Article País de afiliación: Italia 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: Glioblastoma / Hemo-Oxigenasa 1 / Macrófagos Asociados a Tumores Tipo de estudio: Risk_factors_studies Límite: Humans Idioma: En Revista: Int J Cancer Año: 2022 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Estados Unidos