癌症研究
前列腺癌
癌细胞
肿瘤微环境
自然杀伤细胞
免疫学
癌症
化学
免疫系统
细胞毒性T细胞
生物
医学
体外
内科学
生物化学
作者
Kwangsoo Kim,Boreum Choi,Hyunjun Choi,Min Jun Ko,Dong Hwan Kim,Dong-Hyun Kim
标识
DOI:10.1186/s12951-022-01635-y
摘要
Ferroptosis provides an opportunity to overcome the cancer cell therapeutic resistance and modulate the immune system. Here an interaction between ferroptosis of cancer cells and natural killer (NK) cells was investigated with a clinical grade iron oxide nanoparticle (ferumoxytol) for potential synergistic anti-cancer effect of ferroptosis and NK cell therapy in prostate cancer. When ferumoxytol mediated ferroptosis of cancer cells was combined with NK cells, the NK cells' cytotoxic function was increased. Observed ferroptosis mediated NK cell activation was also confirmed with IFN-γ secretion and lytic degranulation. Upregulation of ULBPs, which is one of the ligands for NK cell activating receptor NKG2D, was observed in the co-treatment of ferumoxytol mediated ferroptosis and NK cells. Additionally, HMGB1 and PD-L1 expression of cancer cells were observed in the treatment of ferroptosis + NK cells. Finally, in vivo therapeutic efficacy of ferumoxytol mediated ferroptosis and NK cell therapy was observed with significant tumor volume regression in a prostate cancer mice model. These results suggest that the NK cells' function can be enhanced with ferumoxytol mediated ferroptosis.
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