STING signaling promotes NK cell antitumor immunity and maintains a reservoir of TCF-1+ NK cells.
Cell Rep
; 42(9): 113108, 2023 09 26.
Article
em En
| MEDLINE
| ID: mdl-37708030
ABSTRACT
Natural killer (NK) cells are cytotoxic innate lymphocytes that eradicate tumor cells. Inducing durable antitumor immune responses by NK cells represents a major priority of cancer immunotherapy. While cytosolic DNA sensing plays an essential role in initiating antitumor immunity, the role of NK cell-intrinsic STING signaling remains unclear. Here, we find that NK cell-intrinsic STING promotes antitumor responses and maintains a reservoir of TCF-1+ NK cells. In contrast, tumor cell-intrinsic cGAS and mtDNA are required for NK cell antitumor activity, indicating that tumor mtDNA recognition by cGAS partially triggers NK cell-intrinsic STING activation. Moreover, addition of cGAMP enables STING activation and type I interferon production in NK cells, thereby supporting the activation of NK cells in vitro. In humans, STING agonism promotes the expansion of TCF-1+ NK cells. This study provides insight into understanding how STING signaling drives NK cell antitumor immunity and the development of NK cell-based cancer immunotherapy.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias
/
Antineoplásicos
Limite:
Humans
Idioma:
En
Revista:
Cell Rep
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
China