TY  - JOUR
AU  - Su, Yan
AU  - Huang, Hongyan
AU  - Luo, Tianzhi
AU  - Zheng, You
AU  - Fan, Jie
AU  - Ren, He
AU  - Tang, Meng
AU  - Niu, Zubiao
AU  - Wang, Chenxi
AU  - Wang, Yuqi
AU  - Zhang, Zhengrong
AU  - Liang, Jianqing
AU  - Ruan, Banzhan
AU  - Gao, Lihua
AU  - Chen, Zhaolie
AU  - Melino, Gerry
AU  - Wang, Xiaoning
AU  - Sun, Qiang
TI  - Cell-in-cell structure mediates in-cell killing suppressed by CD44.
JO  - Cell discovery
VL  - 8
IS  - 1
SN  - 2056-5968
CY  - London
PB  - Nature Publishing Group
M1  - DZNE-2022-00620
SP  - 35
PY  - 2022
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:35436988
C2  - pmc:PMC9016064
DO  - DOI:10.1038/s41421-022-00387-1
UR  - https://pub.dzne.de/record/163946
ER  -