Manganese(ii) complexes stimulate antitumor immunity via aggravating DNA damage and activating the cGAS-STING pathway.
Manganese(ii) complexes stimulate antitumor immunity via aggravating DNA damage and activating the cGAS-STING pathway.
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DOI：
10.1039/d2sc06036a
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发表时间：
2023-04-26
期刊：
影响因子：
8.4
通讯作者：
中科院分区：
文献类型：
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作者：
Activating the cyclic GMP-AMP synthase-stimulator of the interferon gene (cGAS-STING) pathway is a promising immunotherapeutic strategy for cancer treatment. Manganese(ii) complexes MnPC and MnPVA (P = 1,10-phenanthroline, C = chlorine, and VA = valproic acid) were found to activate the cGAS-STING pathway. The complexes not only damaged DNA, but also inhibited histone deacetylases (HDACs) and poly adenosine diphosphate-ribose polymerase (PARP) to impede the repair of DNA damage, thereby promoting the leakage of DNA fragments into cytoplasm. The DNA fragments activated the cGAS-STING pathway, which initiated an innate immune response and a two-way communication between tumor cells and neighboring immune cells. The activated cGAS-STING further increased the production of type I interferons and secretion of pro-inflammatory cytokines (TNF-α and IL-6), boosting the tumor infiltration of dendritic cells and macrophages, as well as stimulating cytotoxic T cells to kill cancer cells in vitro and in vivo. Owing to the enhanced DNA-damaging ability, MnPC and MnPVA showed more potent immunocompetence and antitumor activity than Mn2+ ions, thus demonstrating great potential as chemoimmunotherapeutic agents for cancer treatment. Mn complexes act as breakers of DNA to induce DSB, as inhibitors of HDAC and PARP to impede DNA repair, and as activators of the cGAS-STING pathway to trigger immune responses, thereby stimulating T cells to suppress tumor growth in a synergic mechanism.
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影响因子：
4.6
作者：
Gao, Min;Xie, Yu-Qing;Tang, Li
通讯作者：
Tang, Li
DOI：
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发表时间：
2020-02-01
期刊：
哲学分析
影响因子：
--
作者：
马迎辉
通讯作者：
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影响因子：
16.6
作者：
Hayman TJ;Baro M;MacNeil T;Phoomak C;Aung TN;Cui W;Leach K;Iyer R;Challa S;Sandoval-Schaefer T;Burtness BA;Rimm DL;Contessa JN
通讯作者：
Contessa JN
影响因子：
9.7
作者：
Diyabalanage, Himashinie V. K.;Granda, Michael L.;Hooker, Jacob M.
通讯作者：
Hooker, Jacob M.
影响因子：
17.1
作者：
Hou, Lin;Tian, Chunyu;Zhang, Zhenzhong
通讯作者：
Zhang, Zhenzhong