163946 20230915090538.0 10.1038/s41421-022-00387-1 doi pmid:35436988 pmid pmc:PMC9016064 pmc altmetric:126905888 altmetric DZNE-2022-00620 English 610 Su, Yan 0 Cell-in-cell structure mediates in-cell killing suppressed by CD44. London 2022 Nature Publishing Group article DRIVER Output Types/Journal article DataCite Journal Article journal journal PUB:(DE-HGF)16 1655122286_6958 PUB:(DE-HGF) ARTICLE BibTeX JOURNAL_ARTICLE ORCID Journal Article 0 EndNote Penetration of immune cells into tumor cells was believed to be immune-suppressive via cell-in-cell (CIC) mediated death of the internalized immune cells. We unexpectedly found that CIC formation largely led to the death of the host tumor cells, but not the internalized immune cells, manifesting typical features of death executed by NK cells; we named this 'in-cell killing' which displays the efficacy superior to the canonical way of 'kiss-killing' from outside. By profiling isogenic cells, CD44 on tumor cells was identified as a negative regulator of 'in-cell killing' via inhibiting CIC formation. CD44 functions to antagonize NK cell internalization by reducing N-cadherin-mediated intercellular adhesion and by enhancing Rho GTPase-regulated cellular stiffness as well. Remarkably, antibody-mediated blockade of CD44 signaling potentiated the suppressive effects of NK cells on tumor growth associated with increased heterotypic CIC formation. Together, we identified CIC-mediated 'in-cell killing' as a promising strategy for cancer immunotherapy. 351 - Brain Function (POF4-351) G:(DE-HGF)POF4-351 POF4-351 POF IV 0 Dataset connected to CrossRef, PubMed, , Journals: pub.dzne.de Huang, Hongyan 0000-0001-8340-6660 1 Luo, Tianzhi 2 Zheng, You 3 Fan, Jie 4 Ren, He 5 Tang, Meng 6 Niu, Zubiao 7 Wang, Chenxi 8 Wang, Yuqi 9 Zhang, Zhengrong 10 Liang, Jianqing 11 Ruan, Banzhan 12 Gao, Lihua 13 Chen, Zhaolie 14 Melino, Gerry P:(DE-2719)9001390 15 dzne Wang, Xiaoning 16 Sun, Qiang 0000-0002-5342-0637 17 10.1038/s41421-022-00387-1 Vol. 8, no. 1, p. 35 PERI:(DE-600)2842548-0 1 35 Cell discovery 8 2022 2056-5968 OpenAccess http://pub.dzne.de/record/163946/files/DZNE-2022-00620.pdf OpenAccess pdfa http://pub.dzne.de/record/163946/files/DZNE-2022-00620.pdf?subformat=pdfa oai:pub.dzne.de:163946 openaire open_access VDB driver dnbdelivery Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 15 P:(DE-2719)9001390 DE-HGF Gesundheit Neurodegenerative Diseases G:(DE-HGF)POF4-350 G:(DE-HGF)POF4-351 G:(DE-HGF)POF4 G:(DE-HGF)POF4-300 G:(DE-HGF)POF Brain Function 0 2022 Creative Commons Attribution CC BY (No Version) LIC:(DE-HGF)CCBYNV V:(DE-HGF) DOAJ 2021-05-04 DBCoverage StatID:(DE-HGF)1190 StatID Biological Abstracts 2021-05-04 DBCoverage StatID:(DE-HGF)0160 StatID Essential Science Indicators 2021-05-04 WoS StatID:(DE-HGF)0113 StatID Science Citation Index Expanded 2021-05-04 Fees StatID:(DE-HGF)0700 StatID 2021-05-04 OpenAccess StatID:(DE-HGF)0510 StatID Article Processing Charges StatID:(DE-HGF)0561 StatID 2021-05-04 JCR StatID:(DE-HGF)0100 StatID CELL DISCOV : 2021 2022-11-29 DBCoverage StatID:(DE-HGF)0200 StatID SCOPUS 2022-11-29 DBCoverage StatID:(DE-HGF)0300 StatID Medline 2022-11-29 DBCoverage StatID:(DE-HGF)0501 StatID DOAJ Seal 2021-02-14T16:20:07Z DBCoverage StatID:(DE-HGF)0500 StatID DOAJ 2021-02-14T16:20:07Z Peer Review StatID:(DE-HGF)0030 StatID DOAJ : Blind peer review 2021-02-14T16:20:07Z DBCoverage StatID:(DE-HGF)0199 StatID Clarivate Analytics Master Journal List 2022-11-29 DBCoverage StatID:(DE-HGF)0150 StatID Web of Science Core Collection 2022-11-29 DBCoverage StatID:(DE-HGF)1050 StatID BIOSIS Previews 2022-11-29 IF >= 30 StatID:(DE-HGF)9930 StatID CELL DISCOV : 2021 2022-11-29 I:(DE-2719)5000018 AG Nicotera Synaptic Connectivity and Neurodegeneration 0 journal VDB UNRESTRICTED I:(DE-2719)5000018 FullTexts