Targeting CISH enhances natural cytotoxicity receptor signaling and reduces NK cell exhaustion to improve solid tumor immunity.

ABSTRACT:

Background

The success and limitations of current immunotherapies have pushed research toward the development of alternative approaches and the possibility to manipulate other cytotoxic immune cells such as natural killer (NK) cells. Here, we targeted an intracellular inhibiting protein 'cytokine inducible SH2-containing protein' (CISH) in NK cells to evaluate the impact on their functions and antitumor properties.

Methods

To further understand CISH functions in NK cells, we developed a conditional Cish-deficient mouse model in NK cells (Cish^fl/flNcr1^Ki/+ ). NK cells cytokine expression, signaling and cytotoxicity has been evaluated in vitro. Using intravenous injection of B16F10 melanoma cell line and EO711 triple negative breast cancer cell lin

SUBMITTER: Bernard PL 

PROVIDER: S-EPMC9121483 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature