Delivery of IL2RG mRNA via nanoparticles to enhance CD8+ T cell promotes anti-tumor effects against late-stage triple-negative breast cancer
Year: 2024
Type: article
Abstract: The manipulation of CD8 + T cell functions through genetic modifications presents a novel approach to cancer immunotherapy. This study aimed to explore the effects of IL2RG-overexpressing CD8 + T cells and assess the efficacy of delivering IL2RG mRNA via nanoparticles (NPs) to the tumor microenvironment in triple-negative breast cancer (TNBC). Single-cell RNA sequencing (scRNA-seq) was conducted on tissue from early and late-stage TNBC, followed by a meta-analysis of six breast cancer arrays from the GEO database to identify candidate genes. CRISPR/Cas9 was employed for gene knockout and overexpression in CD8 + T cells, which were then analyzed using flow cytometry, ELISA, immunofluorescence, and metabolic assays. A 3D cancer cell spheroid model was used for co-culture experiments. Lipid-coated calcium-phosphate (LCP)@IL2RG NPs were synthesized and injected into TNBC mouse models. IL2RG was identified as significantly associated with late-stage TNBC. Overexpression of IL2RG in CD8 + T cells led to increased cell activation, cytotoxicity, and glycolysis, while knockout reduced these effects. Overexpressing IL2RG in CD8 + T cells co-cultured with 3D cancer spheroids resulted in enhanced apoptosis and reduced cancer cell invasion. Injection of LCP@IL2RG NPs into TNBC mouse models significantly mitigated tumor growth. Overexpressing IL2RG in CD8 + T cells enhances tumor immunotherapy. Delivering IL2RG mRNA via NPs further amplifies this effect, offering a promising strategy for the treatment of late-stage TNBC.
Source: Cancer Nanotechnology
Authors: Ying Li, Fang Huang, Ruoying Deng, Da Jiang
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $1,890
OpenAlex ID: W4403639094