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000163946 1001_ $$aSu, Yan$$b0
000163946 245__ $$aCell-in-cell structure mediates in-cell killing suppressed by CD44.
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000163946 520__ $$aPenetration 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.
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000163946 7001_ $$00000-0001-8340-6660$$aHuang, Hongyan$$b1
000163946 7001_ $$aLuo, Tianzhi$$b2
000163946 7001_ $$aZheng, You$$b3
000163946 7001_ $$aFan, Jie$$b4
000163946 7001_ $$aRen, He$$b5
000163946 7001_ $$aTang, Meng$$b6
000163946 7001_ $$aNiu, Zubiao$$b7
000163946 7001_ $$aWang, Chenxi$$b8
000163946 7001_ $$aWang, Yuqi$$b9
000163946 7001_ $$aZhang, Zhengrong$$b10
000163946 7001_ $$aLiang, Jianqing$$b11
000163946 7001_ $$aRuan, Banzhan$$b12
000163946 7001_ $$aGao, Lihua$$b13
000163946 7001_ $$aChen, Zhaolie$$b14
000163946 7001_ $$0P:(DE-2719)9001390$$aMelino, Gerry$$b15$$udzne
000163946 7001_ $$aWang, Xiaoning$$b16
000163946 7001_ $$00000-0002-5342-0637$$aSun, Qiang$$b17
000163946 773__ $$0PERI:(DE-600)2842548-0$$a10.1038/s41421-022-00387-1$$gVol. 8, no. 1, p. 35$$n1$$p35$$tCell discovery$$v8$$x2056-5968$$y2022
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