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

Abstract

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.

• Authors: Xing Li, Jie Chen, Yong-Jian Chen, Yi-Dan Qiao, Li-Yun Zhao, Nan Jiang, Xiang-Yuan Wu, Yan-Fang Xing
• Journal: Communications biology (Commun Biol) Vol. 4 Issue 1 Pg. 252 (02 26 2021) ISSN: 2399-3642 [Electronic] England
• PMID: 33637832 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Bleomycin
• Dexamethasone
• Ovalbumin
• Lactoferrin
• Cisplatin

Topics

• Acute Kidney Injury (chemically induced, immunology, metabolism, therapy)
• Adoptive Transfer
• Animals
• Anti-Inflammatory Agents (pharmacology)
• Bleomycin
• Cell Line, Tumor
• Cisplatin
• Dexamethasone (pharmacology)
• Disease Models, Animal
• Drug Therapy, Combination
• Female
• Humans
• Lactoferrin (pharmacology)
• Lung Diseases, Interstitial (chemically induced, immunology, metabolism, therapy)
• Male
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Myeloid-Derived Suppressor Cells (drug effects, immunology, metabolism, transplantation)
• Ovalbumin
• Phenotype
• Pneumonia (chemically induced, immunology, metabolism, therapy)
• Mice