A bimetallic nanoplatform for STING activation and CRISPR/Cas mediated depletion of the methionine transporter in cancer cells restores anti-tumor immune responses.

ABSTRACT: Lack of sufficient cytotoxic T lymphocytes (CD8⁺ T cells) infiltration and dysfunctional state of CD8⁺ T cells are considered enormous obstacles to antitumor immunity. Herein, we construct a synergistic nanoplatform to promote CD8⁺ T cell infiltration in tumors while restoring T cell function by regulating methionine metabolism and activating the STING innate immune pathway. The CRISPR/Cas9 system down-regulates the methionine transporter SLC43A2 and restricts the methionine uptake by tumor cells, thereby relieving the methionine competition pressure of T cells; simultaneously, the released nutrition metal ions activate the cGAS/STING pathway. In this work, the described nanoplatform can enhance the effect of immunotherapy in preclinical cancer models in fe

SUBMITTER: Huang Y 

PROVIDER: S-EPMC10397352 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature