Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Center for Data Sciences, Brigham and Women's Hospital, Boston, MA, USA.
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.
经典树突状细胞（cDC）是调节免疫和耐受的专业抗原提呈细胞（APC）。在人类疾病和用细胞因子培养中性粒细胞后，观察到具有 DC 特性的中性粒细胞来源细胞（nAPC）。在这里，我们表明，FcγR 介导的抗体-抗原复合物或抗 FcγRIIIB-抗原缀合物的内吞作用将中性粒细胞转化为 nAPC，与仅用细胞因子生成的 nAPC 相比，它们能将 T 细胞激活到与 cDC 观察到的水平，并在小鼠中引发 CD8 T 细胞依赖性抗肿瘤免疫。单细胞转录分析和验证研究表明，转录因子 PU.1 参与中性粒细胞向 nAPC 的转化。在人类中，狼疮患者血液中 nAPC 的频率与疾病相关。此外，抗 FcγRIIIB-抗原缀合物治疗可诱导 nAPC，当使用携带新抗原的骨髓肿瘤个体或接种细菌毒素疫苗的个体的中性粒细胞时，这些 nAPC 可以激活自身 T 细胞。因此，抗 FcγRIIIB-抗原缀合物诱导的中性粒细胞向免疫原性 nAPC 的转化可能代表癌症和传染病的一种潜在免疫疗法。
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