Dexamethasone and lactoferrin induced PMN-MDSCs relieved inflammatory adverse events of anti-cancer therapy without tumor promotion

Li, Xing1,2; Chen, Jie1,2; Chen, Yong-Jian1,2; Qiao, Yi-Dan1,2; Zhao, Li-Yun1,2; Jiang, Nan3,4; Wu, Xiang-Yuan1,2; Xing, Yan-Fang5

2021-02-26

10.1038/s42003-021-01769-z

COMMUNICATIONS BIOLOGY   影响因子和分区

2399-3642

In this era of immune checkpoint inhibitors, inflammatory adverse events of anti-cancer therapies continue to pose a major challenge. Glucocorticoids, as the mainstay, were limited by serious side effects. Glucocorticoids induce myeloid-derived suppressor cells (MDSCs), and lactoferrin-induced polymorphonuclear MDSCs (PMN-MDSCs) were shown to relieve inflammatory conditions. Combined treatment with dexamethasone (DXM) and lactoferrin increased the generation of PMN-MDSCs in vitro (DXM/lactoferrin PMN-MDSCs) compared to DXM or lactoferrin treatment alone. DXM/lactoferrin PMN-MDSCs were distinct from tumor PMN-MDSCs in vivo with regard to gene expression profiles. DXM upregulated the myeloid cell response to lactoferrin by inducing the lactoferrin receptor Lrp1. DXM/lactoferrin PMN-MDSCs presented anti-bacterial capability, increased PGE2 production, increased survival capability, and decreased tumor tissue homing. Transfer of DXM/lactoferrin PMN-MDSCs relieved cisplatin-induced acute kidney failure, bleomycin-induced interstitial pneumonia, and allergic pneumonitis effectively without promoting tumor development. Our study shows that DXM/lactoferrin PMN-MDSCs are a promising cell therapy for inflammatory adverse events of anti-cancer therapies. Li et al. show that dexamethasone and lactoferrin induced polymorphonuclear myeloid-derived suppressor cells relieve inflammatory conditions in mouse models with minimal effect on tumour growth. This work demonstrates promise for combating inflammatory adverse events during anti-cancer treatments.

SCI

英语

其他

Guangdong Basic and Applied Basic Research Foundation["2019A1515012198","2019A1515011187","2017A030313537"] ; Guangzhou Science and Technology Project[201904010461] ; National Natural Science Foundation of China[81972677,81871999,81700645] ; Special Fundamental Research Fund of Sun Yat-sen University[19ykpy17] ; Tip-top Scientific and Technical Innovative Youth Talents of Guangdong Special Support Program[2019TQ05Y266]

Life Sciences & Biomedicine - Other Topics ; Science & Technology - Other Topics

Biology ; Multidisciplinary Sciences

WOS:000624657700004

NATURE RESEARCH

Web of Science

1.Sun Yat Sen Univ, Affiliated Hosp 3, Dept Med Oncol, 600 Tianhe Rd, Guangzhou 510630, Peoples R China
2.Sun Yat Sen Univ, Affiliated Hosp 3, Guangdong Key Lab Liver Dis Res, 600 Tianhe Rd, Guangzhou 510630, Peoples R China
3.Southern Univ Sci & Technol, Affiliated Hosp 2, Dept Transplantat, 29th Bulan Rd, Shenzhen 510623, Peoples R China
4.Third Peoples Hosp Shenzhen, 29th Bulan Rd, Shenzhen 510623, Peoples R China
5.Guangzhou Med Univ, Affiliated Hosp 3, Dept Nephrol, 63 Duobao Rd, Guangzhou 510150, Peoples R China

Li, Xing,Chen, Jie,Chen, Yong-Jian,et al. Dexamethasone and lactoferrin induced PMN-MDSCs relieved inflammatory adverse events of anti-cancer therapy without tumor promotion[J]. COMMUNICATIONS BIOLOGY,2021,4(1).

Li, Xing.,Chen, Jie.,Chen, Yong-Jian.,Qiao, Yi-Dan.,Zhao, Li-Yun.,...&Xing, Yan-Fang.(2021).Dexamethasone and lactoferrin induced PMN-MDSCs relieved inflammatory adverse events of anti-cancer therapy without tumor promotion.COMMUNICATIONS BIOLOGY,4(1).

Li, Xing,et al."Dexamethasone and lactoferrin induced PMN-MDSCs relieved inflammatory adverse events of anti-cancer therapy without tumor promotion".COMMUNICATIONS BIOLOGY 4.1(2021).