肿瘤微环境
流式细胞术
免疫系统
免疫疗法
癌症研究
肽
受体
癌症免疫疗法
甲酰肽受体
活性氧
免疫学
癌细胞
化学
癌症
生物
趋化性
细胞生物学
生物化学
遗传学
作者
Sun Haixia,Shuxin Li,Qiao-Li Wang,Chunxiang Luo,Lan‐Yi Zhong,Guohui Wan,Ziqian Li,Gexin Zhao,Xianzhang Bu,Mu‐Sheng Zeng,Guo‐Kai Feng
标识
DOI:10.1016/j.biopha.2024.116670
摘要
Neutrophils are heterogeneous and plastic, with the ability to polarize from antitumour to protumour phenotype and modulate tumour microenvironment components. While some advances have been made, the neutrophil-targeting therapy remains underexplored. Activation of formyl peptide receptors (FPRs) by formylated peptides is needed for local control of infection through the recruitment of activated neutrophils while the potential contribution of antitumour activity remains underexplored. Here, we demonstrate that neutrophils can be harnessed to suppress tumour growth through the action of the formyl peptide (FP) on the formyl peptide receptor (FPR). Mechanistically, FP efficiently recruits neutrophils to produce reactive oxygen species production (ROS), resulting in the direct killing of tumours. Antitumour functions disappeared when neutrophils were depleted by anti-Ly6G antibodies. Interestingly, extensive T-cell activation was observed in mouse tumours treated with FP, showing the potential to alter the immune suppressed tumour microenvironment (TME) and further sensitize mice to anti-PD1 therapy. Transcriptomic and flow cytometry analyses revealed the mechanisms of FP-sensitized anti-PD1 therapy, mainly including stimulated neutrophils and an altered immune-suppressed tumour microenvironment. Collectively, these data establish FP as an effective combination partner for sensitizing anti-PD1 therapy by stimulating tumour-infiltrated neutrophils.
科研通智能强力驱动
Strongly Powered by AbleSci AI