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FcγR engagement reprograms neutrophils into antigen cross-presenting cells that elicit acquired anti-tumor immunity.
Mysore, Vijayashree; Cullere, Xavier; Mears, Joseph; Rosetti, Florencia; Okubo, Koshu; Liew, Pei X; Zhang, Fan; Madera-Salcedo, Iris; Rosenbauer, Frank; Stone, Richard M; Aster, Jon C; von Andrian, Ulrich H; Lichtman, Andrew H; Raychaudhuri, Soumya; Mayadas, Tanya N.
Afiliação
  • Mysore V; Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Cullere X; Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Mears J; Center for Data Sciences, Brigham and Women's Hospital, Boston, MA, USA.
  • Rosetti F; Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Okubo K; Division of Rheumatology, Immunology, Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Liew PX; Departamento de Inmunología y Reumatología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
  • Zhang F; Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Madera-Salcedo I; Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Rosenbauer F; Center for Data Sciences, Brigham and Women's Hospital, Boston, MA, USA.
  • Stone RM; Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Aster JC; Division of Rheumatology, Immunology, Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • von Andrian UH; Departamento de Inmunología y Reumatología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
  • Lichtman AH; Institute of Molecular Tumor Biology, University of Muenster, Muenster, Germany.
  • Raychaudhuri S; Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
  • Mayadas TN; Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Nat Commun ; 12(1): 4791, 2021 08 09.
Article em En | MEDLINE | ID: mdl-34373452
ABSTRACT
Classical dendritic cells (cDC) are professional antigen-presenting cells (APC) that regulate immunity and tolerance. Neutrophil-derived cells with properties of DCs (nAPC) are observed in human diseases and after culture of neutrophils with cytokines. Here we show that FcγR-mediated endocytosis of antibody-antigen complexes or an anti-FcγRIIIB-antigen conjugate converts neutrophils into nAPCs that, in contrast to those generated with cytokines alone, activate T cells to levels observed with cDCs and elicit CD8+ T cell-dependent anti-tumor immunity in mice. Single cell transcript analyses and validation studies implicate the transcription factor PU.1 in neutrophil to nAPC conversion. In humans, blood nAPC frequency in lupus patients correlates with disease. Moreover, anti-FcγRIIIB-antigen conjugate treatment induces nAPCs that can activate autologous T cells when using neutrophils from individuals with myeloid neoplasms that harbor neoantigens or those vaccinated against bacterial toxins. Thus, anti-FcγRIIIB-antigen conjugate-induced conversion of neutrophils to immunogenic nAPCs may represent a possible immunotherapy for cancer and infectious diseases.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Receptores de IgG / Antígenos de Neoplasias / Neoplasias / Neutrófilos Idioma: En Ano de publicação: 2021 Tipo de documento: Article
Texto completo
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XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Receptores de IgG / Antígenos de Neoplasias / Neoplasias / Neutrófilos Idioma: En Ano de publicação: 2021 Tipo de documento: Article