Translocator protein-targeted photodynamic therapy for direct and abscopal immunogenic cell death in colorectal cancer.
Translocator protein-targeted photodynamic therapy for direct and abscopal immunogenic cell death in colorectal cancer.
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DOI：
10.1016/j.actbio.2021.07.052
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发表时间：
2021-10-15
影响因子：
9.7
通讯作者：
Bai M
中科院分区：
文献类型：
--
作者：
Xie Q;Li Z;Liu Y;Zhang D;Su M;Niitsu H;Lu Y;Coffey RJ;Bai M
远位效应是一种有吸引力的癌症治疗效果，指的是远离主要治疗部位的位置处的肿瘤消退。免疫原性细胞死亡（ICD）通过激活有利的抗肿瘤免疫应答，在原发性和远期治疗效果之间提供了机制联系。在这项研究中，我们通过靶向18 kDa转运蛋白（TSPO）（一种在CRC中过表达的线粒体受体），在体外和体内诱导结直肠癌（CRC）细胞系中的ICD。使用TSPO靶向光敏剂IR 700DX-6 T的光动力疗法（PDT）在14个CRC细胞系中引起有效的凋亡性细胞死亡。在同基因免疫活性CRC小鼠模型中，经受TSPO-PDT的肿瘤的生长被极大地抑制。值得注意的是，对侧腹中未治疗的肿瘤也显示出显著的生长抑制。树突状细胞和CD 8 + T细胞在TSPO-PDT治疗后被激活，伴随着治疗和未治疗肿瘤中Treg细胞的减少。此外，由TSPO-PDT开发的癌症疫苗产生了显著的肿瘤抑制效果。这些结果表明，TSPO-PDT不仅可以直接抑制肿瘤生长，而且还可以显著地激发宿主抗肿瘤免疫，突出了TSPO-PDT作为表现出全身效应的CRC的成功治疗剂的潜力。
Abscopal effect is an attractive cancer therapeutic effect referring to tumor regression at a location distant from the primary treatment site. Immunogenic cell death (ICD) offers a mechanistic link between the primary and remote therapeutic effects by activating favorable anti-tumor immune responses. In this study, we induced ICD in colorectal cancer (CRC) cell lines in vitro and in vivo by targeting the 18 kDa translocator protein (TSPO), a mitochondrial receptor overexpressed in CRC. Photodynamic therapy (PDT) using a TSPO-targeted photosensitizer, IR700DX-6T, caused effective apoptotic cell death in fourteen CRC cell lines. In a syngeneic immunocompetent CRC mouse model, the growth of tumors subjected to TSPO-PDT was greatly suppressed. Remarkably, untreated tumors in the opposing flank also showed marked growth suppression. Dendritic and CD8+ T cells were activated after TSPO-PDT treatment, accompanied by decreased Treg cells in both treated and non-treated tumors. In addition, a cancer vaccine developed from TSPO-PDT produced a significant tumor inhibition effect. These results indicate that TSPO-PDT could not only directly suppress tumor growth but also dramatically provoke host anti-tumor immunity, highlighting the potential of TSPO-PDT as a successful therapeutic for CRC that exhibits systemic effects.
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影响因子：
5.8
作者：
Garg, Abhishek D.;Krysko, Dmitri V.;Agostinis, Patrizia
通讯作者：
Agostinis, Patrizia
DOI：
10.1158/1078-0432.ccr-13-1735
发表时间：
2013-12-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Rigual N;Shafirstein G;Cooper MT;Baumann H;Bellnier DA;Sunar U;Tracy EC;Rohrbach DJ;Wilding G;Tan W;Sullivan M;Merzianu M;Henderson BW
通讯作者：
Henderson BW
近红外光触发药物输送系统可提高化学光热联合治疗的疗效
影响因子：
9.7
作者：
Chen, Yi;Li, Haohuan;Ci, Tianyuan
通讯作者：
Ci, Tianyuan
影响因子：
2.8
作者：
Han, ZQ;Slack, RS;Papadopoulos, V
通讯作者：
Papadopoulos, V
DOI：
10.1007/978-94-007-2869-1_7
发表时间：
2012-01-01
期刊：
ADVANCES IN MITOCHONDRIAL MEDICINE
影响因子：
--
作者：
Estaquier, Jerome;Vallette, Francois;Mignotte, Bernard
通讯作者：
Mignotte, Bernard