Enhanced natural killer cell anti-tumor activity with nanoparticles mediated ferroptosis and potential therapeutic application in prostate cancer.
Enhanced natural killer cell anti-tumor activity with nanoparticles mediated ferroptosis and potential therapeutic application in prostate cancer.
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DOI：
10.1186/s12951-022-01635-y
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发表时间：
2022-09-29
影响因子：
10.2
通讯作者：
Kim, Dong-Hyun
中科院分区：
文献类型：
--
作者：
Kim, Kwang-Soo;Choi, Bongseo;Choi, Hyunjun;Ko, Min Jun;Kim, Dong-Hwan;Kim, Dong-Hyun
铁凋亡提供了克服癌细胞治疗抗性和调节免疫系统的机会。在此，用临床级氧化铁纳米颗粒（ferumoxytol）研究了癌细胞的铁凋亡和自然杀伤（NK）细胞之间的相互作用，以获得铁凋亡和NK细胞疗法在前列腺癌中的潜在协同抗癌作用。当ferumoxytol介导的癌细胞铁凋亡与NK细胞结合时，NK细胞的细胞毒作用增强。观察到的铁凋亡介导的NK细胞活化也通过IFN-γ分泌和溶解性脱粒得到证实。在ferumoxytol介导的铁凋亡和NK细胞的共处理中观察到ULBP的上调，ULBP是NK细胞活化受体NKG 2D的配体之一。此外，在铁凋亡+ NK细胞治疗中观察到癌细胞的HMGB 1和PD-L1表达。最后，在前列腺癌小鼠模型中观察到ferumoxytol介导的铁凋亡和NK细胞疗法的体内治疗功效，具有显著的肿瘤体积消退。这些结果表明，ferumoxytol介导的铁凋亡可以增强NK细胞的功能。在线版本包含补充材料，可通过10.1186/s12951-022-01635-y获得。
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. The online version contains supplementary material available at 10.1186/s12951-022-01635-y.
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DOI：
10.1073/pnas.1415518111
发表时间：
2014-11-25
影响因子：
11.1
作者：
Linkermann, Andreas;Skouta, Rachid;Krautwald, Stefan
通讯作者：
Krautwald, Stefan
影响因子：
15.9
作者：
Alkins, Ryan;Burgess, Alison;Hynynen, Kullervo
通讯作者：
Hynynen, Kullervo
DOI：
10.1007/978-1-0716-0247-8_11
发表时间：
2020-01-01
期刊：
IMMUNE MEDIATORS IN CANCER: METHODS AND PROTOCOLS
影响因子：
--
作者：
Martinez, Alejandra M.;Kim, Ahryun;Yang, Wan Seok
通讯作者：
Yang, Wan Seok
影响因子：
5.4
作者：
Kim KS;Kim DH;Kim DH
通讯作者：
Kim DH
影响因子：
8.8
作者：
Garcia-Diaz A;Shin DS;Moreno BH;Saco J;Escuin-Ordinas H;Rodriguez GA;Zaretsky JM;Sun L;Hugo W;Wang X;Parisi G;Saus CP;Torrejon DY;Graeber TG;Comin-Anduix B;Hu-Lieskovan S;Damoiseaux R;Lo RS;Ribas A
通讯作者：
Ribas A