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	Oncolysis with DTT-205 and DTT-304 generates immunological memory in cured animals
	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
	2018-10-23
卷号	9页码:14
ISSN号	2041-4889
DOI	10.1038/s41419-018-1127-3
通讯作者	Kepp, Oliver(captain.olsen@gmail.com) ; Kroemer, Guido(kroemer@orange.fr)
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.
收录类别	SCI
WOS关键词	MITOCHONDRIAL-MEMBRANE PERMEABILIZATION ; IMMUNOGENIC CELL-DEATH ; HOST-DEFENSE PEPTIDES ; CANCER-CELLS ; LTX-315 ; IMMUNOTHERAPY ; CHEMOTHERAPY ; NECROSIS ; IMMUNITY ; TUMOR
WOS研究方向	Cell Biology
WOS类目	Cell Biology
语种	英语
出版者	NATURE PUBLISHING GROUP
WOS记录号	WOS:000448194000001
内容类型	期刊论文
URI标识	http://www.corc.org.cn/handle/1471x/2558281
专题	寒区旱区环境与工程研究所
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,2018,9:14.
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,9,14.
MLA	Zhou, Heng,et al."Oncolysis with DTT-205 and DTT-304 generates immunological memory in cured animals".CELL DEATH & DISEASE 9(2018):14.

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