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Abstract
The study evaluates 36 CAR formats in macrophage-targeted mRNA lipid nanoparticles.
- Tailored CAR macrophages with CD3ζ TLR4 intracellular domains stimulate strong adaptive immune responses.
- These CAR macrophages significantly enhance the effectiveness of PD-1/L1 therapy.
- Single-cell RNA sequencing indicates that CAR macrophages alter the tumor microenvironment to become less immunosuppressive.
- CAR macrophages increase the population of progenitor-exhausted CD8 T cells, which are crucial for anti-tumor immunity.
- Mechanistically, CAR macrophages promote a proinflammatory state and enhance the expression of MHC-I and PD-L1 through NF-κB pathway modulation.
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