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

Vijayashree Mysore, Xavier Cullere, Joseph Mears, Florencia Rosetti, Koshu Okubo, Pei X. Liew, Fan Zhang, Iris Madera-Salcedo, Frank Rosenbauer, Richard M. Stone, Jon C. Aster, Ulrich H. von Andrian, Andrew H. Lichtman, Soumya Raychaudhuri and Tanya N. Mayadas ()
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Vijayashree Mysore: Brigham and Women’s Hospital and Harvard Medical School
Xavier Cullere: Brigham and Women’s Hospital and Harvard Medical School
Joseph Mears: Brigham and Women’s Hospital
Florencia Rosetti: Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
Koshu Okubo: Brigham and Women’s Hospital and Harvard Medical School
Pei X. Liew: Brigham and Women’s Hospital and Harvard Medical School
Fan Zhang: Brigham and Women’s Hospital
Iris Madera-Salcedo: Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
Frank Rosenbauer: University of Muenster
Richard M. Stone: Dana-Farber Cancer Institute and Harvard Medical School
Jon C. Aster: Brigham and Women’s Hospital and Harvard Medical School
Ulrich H. von Andrian: Harvard Medical School
Andrew H. Lichtman: Brigham and Women’s Hospital and Harvard Medical School
Soumya Raychaudhuri: Brigham and Women’s Hospital
Tanya N. Mayadas: Brigham and Women’s Hospital and Harvard Medical School

Nature Communications, 2021, vol. 12, issue 1, 1-23

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-24591-x

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