Cell-in-cell structure mediates in-cell killing suppressed by CD44.
Journal
Cell discovery
ISSN: 2056-5968
Titre abrégé: Cell Discov
Pays: England
ID NLM: 101661034
Informations de publication
Date de publication:
19 Apr 2022
19 Apr 2022
Historique:
received:
18
07
2021
accepted:
28
01
2022
entrez:
19
4
2022
pubmed:
20
4
2022
medline:
20
4
2022
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 35436988
doi: 10.1038/s41421-022-00387-1
pii: 10.1038/s41421-022-00387-1
pmc: PMC9016064
doi:
Types de publication
Journal Article
Langues
eng
Pagination
35Subventions
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 31970685
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 81872314
Informations de copyright
© 2022. The Author(s).
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