FcγR engagement reprograms neutrophils into antigen cross-presenting cells that elicit acquired anti-tumor immunity

Nat Commun. 2021 Aug 9;12(1):4791. doi: 10.1038/s41467-021-24591-x.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Vesicular Transport / genetics
  • Animals
  • Antigen Presentation / immunology
  • Antigen-Antibody Complex
  • Antigens, Neoplasm / immunology*
  • Bone Marrow
  • CD4-Positive T-Lymphocytes
  • CD8-Positive T-Lymphocytes
  • Cell Movement
  • Cell Proliferation
  • Cytokines / immunology
  • Dendritic Cells / immunology
  • Endocytosis
  • Humans
  • Immunity, Innate
  • Immunotherapy
  • Lymph Nodes / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myeloid Differentiation Factor 88 / genetics
  • Neoplasms / immunology*
  • Neutrophils / immunology*
  • Reactive Oxygen Species
  • Receptors, IgG / genetics*
  • Receptors, IgG / immunology*
  • Transcriptome


  • Adaptor Proteins, Vesicular Transport
  • Antigen-Antibody Complex
  • Antigens, Neoplasm
  • Cytokines
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • Reactive Oxygen Species
  • Receptors, IgG
  • TICAM-1 protein, mouse