Oncolysis with DTT-205 and DTT-304 generates immunological memory in cured animals
文献类型：期刊论文
| 作者 | Zhou, Heng1,2,3,4,18; Mondragon, Laura1,2,3,4; Xie, Wei1,2,3,4; Mauseth, Brynjar5,6,7; Leduc, Marion1,2,3,4; Sauvat, Allan1,2,3,4; Gomes-da-Silva, Ligia C.1,2,3,4,8; Forveille, Sabrina1,2,3,4; Iribarren, Kristina1,2,3,4; Souquere, Sylvie9,10 |
| 刊名 | CELL DEATH & DISEASE
 |
| 出版日期 | 2018-10-23 |
| 卷号 | 9 |
| ISSN号 | 2041-4889 |
| DOI | 10.1038/s41419-018-1127-3 |
| 英文摘要 | Oncolytic peptides and peptidomimetics are being optimized for the treatment of cancer by selecting agents with high cytotoxic potential to kill a maximum of tumor cells as well as the capacity to trigger anticancer immune responses and hence to achieve long-term effects beyond therapeutic discontinuation. Here, we report on the characterization of two novel oncolytic peptides, DTT-205 and DTT-304 that both selectively enrich in the lysosomal compartment of cancer cells yet differ to some extent in their cytotoxic mode of action. While DTT-304 can trigger the aggregation of RIP3 in ripoptosomes, coupled to the phosphorylation of MLKL by RIP3, DTT-205 fails to activate RIP3. Accordingly, knockout of either RIP3 or MLKL caused partial resistance against cell killing by DTT-304 but not DTT-205. In contrast, both agents shared common features in other aspects of pro-death signaling in the sense that their cytotoxic effects were strongly inhibited by both serum and antioxidants, partially reduced by lysosomal inhibition with bafilomycin Al or double knockout of Bax and Bak, yet totally refractory to caspase inhibition. Both DTT-304 and DTT-205 caused the exposure of calreticulin at the cell surface, as well as the release of HMGB1 from the cells. Mice bearing established subcutaneous cancers could be cured by local injection of DTT-205 or DTT-304, and this effect depended on T lymphocytes, as it led to the establishment of a long-term memory response against tumor-associated antigens. Thus, mice that had been cured from cancer by the administration of DTT compounds were refractory against rechallenge with the same cancer type several months after the disappearance of the primary lesion. In summary, DTT-205 and DTT-304 both have the capacity to induce immunotherapeutic oncolysis. |
| WOS关键词 | MITOCHONDRIAL-MEMBRANE PERMEABILIZATION ; IMMUNOGENIC CELL-DEATH ; HOST-DEFENSE PEPTIDES ; CANCER-CELLS ; LTX-315 ; IMMUNOTHERAPY ; CHEMOTHERAPY ; NECROSIS ; IMMUNITY ; TUMOR |
| 资助项目 | Portuguese Science Foundation[SFRH/BPD/93562/2013] |
| WOS研究方向 | Cell Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:000448194000001 |
| 出版者 | NATURE PUBLISHING GROUP |
| 源URL | [http://119.78.100.186/handle/113462/64410]  |
| 专题 | 中国科学院近代物理研究所 |
| 通讯作者 | Kepp, Oliver; Kroemer, Guido |
| 作者单位 | 1.Gustave Roussy Comrehens Canc Inst, Metabol & Cell Biol Platforms, Villejuif, France 2.INSERM U, Ctr Rech Cordeliers, Equipe Labellisee Ligue Canc 11, F-1138 Paris, France 3.Univ Paris 05, Sorbonne Paris Cite, Paris, France 4.Univ Paris 06, Paris, France 5.Lytix Biopharma, Oslo, Norway 6.Oslo Univ Hosp, Rikshosp, Div Canc Surg & Transplantat, Oslo, Norway 7.Univ Oslo, Inst Clin Med, Oslo, Norway 8.Univ Coimbra, Chem Dept, Coimbra, Portugal 9.Gustave Roussy Comprehens Canc Ctr, Villejuif, France 10.CNRS, UMR9196, Villejuif, France |
| 推荐引用方式 GB/T 7714 | Zhou, Heng,Mondragon, Laura,Xie, Wei,et al. Oncolysis with DTT-205 and DTT-304 generates immunological memory in cured animals[J]. CELL DEATH & DISEASE,2018,9. |
| APA | Zhou, Heng.,Mondragon, Laura.,Xie, Wei.,Mauseth, Brynjar.,Leduc, Marion.,...&Kroemer, Guido.(2018).Oncolysis with DTT-205 and DTT-304 generates immunological memory in cured animals.CELL DEATH & DISEASE,9. |
| MLA | Zhou, Heng,et al."Oncolysis with DTT-205 and DTT-304 generates immunological memory in cured animals".CELL DEATH & DISEASE 9(2018). |
入库方式： OAI收割
来源：近代物理研究所
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