Department of Medical Oncology and Guangdong Key laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen University, 600 Tianhe Road, Guangzhou, 510630, PR China.
Department of Transplantation, the Second Affiliated Hospital of Southern University of Science and Technology and the Third People's Hospital of Shenzhen, 29th Bulan Road, Shenzhen, 510623, PR China.
Commun Biol. 2021 Feb 26;4(1):252. doi: 10.1038/s42003-021-01769-z.
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.
在免疫检查点抑制剂时代，癌症治疗的炎症不良反应仍然是一个主要挑战。糖皮质激素作为主要药物，受到严重副作用的限制。糖皮质激素诱导髓源抑制细胞（MDSCs），而乳铁蛋白诱导的多形核 MDSCs（PMN-MDSCs）被证明可以缓解炎症状态。与单独使用地塞米松（DXM）或乳铁蛋白相比，DXM 和乳铁蛋白联合治疗可增加体外 PMN-MDSCs 的生成（DXM/乳铁蛋白 PMN-MDSCs）。DXM/乳铁蛋白 PMN-MDSCs 在基因表达谱方面与体内肿瘤 PMN-MDSCs 不同。DXM 通过诱导乳铁蛋白受体 Lrp1 来上调髓细胞对乳铁蛋白的反应。DXM/乳铁蛋白 PMN-MDSCs 具有抗细菌能力，增加 PGE2 的产生，提高生存能力，并减少肿瘤组织归巢。转移 DXM/乳铁蛋白 PMN-MDSCs 可有效缓解顺铂诱导的急性肾衰竭、博来霉素诱导的间质性肺炎和过敏性肺炎，而不会促进肿瘤发展。我们的研究表明，DXM/乳铁蛋白 PMN-MDSCs 是一种有前途的癌症治疗炎症不良反应的细胞疗法。
