Sustained effector function of IL-12/15/18-preactivated NK cells against established tumors.
J Exp Med
; 209(13): 2351-65, 2012 Dec 17.
Article
em En
| MEDLINE
| ID: mdl-23209317
ABSTRACT
Natural killer cell (NK cell)-based immunotherapy of cancer is hampered by the transient effector function of NK cells. Recently, mouse IL-12/15/18-preactivated NK cells were shown to persist with sustained effector function in vivo. Our study investigated the antitumor activity of such NK cells. A single injection of syngeneic IL-12/15/18-preactivated NK cells, but neither naive nor IL-15- or IL-2-pretreated NK cells, combined with irradiation substantially reduced growth of established mouse tumors. Radiation therapy (RT) was essential for the antitumor activity of transferred NK cells. IL-12/15/18-preactivated NK cells expressed high levels of IL-2Rα (CD25), and their rapid in vivo proliferation depended on IL-2 produced by CD4+ T cells. IL-12/15/18-preactivated NK cells accumulated in the tumor tissue and persisted at high cell numbers with potent effector function that required the presence of CD4+ T cells. RT greatly increased numbers and function of transferred NK cells. Human IL-12/15/18-preactivated NK cells also displayed sustained effector function in vitro. Our study provides a better understanding for the rational design of immunotherapies of cancer that incorporate NK cells. Moreover, our results reveal an essential role of CD4+ T cell help for sustained antitumor activity by NK cells linking adaptive and innate immunity.
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1
Base de dados:
MEDLINE
Assunto principal:
Células Matadoras Naturais
/
Imunoterapia Adotiva
/
Neoplasias Experimentais
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article