CELL INTELLIGENCE · 肿瘤细胞治疗研究

Adoptive cell therapy with macrophages holds great promise for treating solid tumors, but its clinical impact has been limited. The problem is twofold: the immunosuppressive tumor microenvironment quickly silences the anti-tumor activity of transferred cells, and systemic activation strategies often provoke off-target toxicity. Here, we describe a simple yet effective approach to overcome these barriers. We engineered primary macrophages with anti-CD11b-functionalized zinc-aluminum layered double hydroxide micropatches (LDHMP)-a surface-anchoring strategy that leaves the cells otherwise unaltered. Once the engineered cells (Mip@MΦ) reach the acidic tumor microenvironment, the micropatches degrade, releasing Zn 2+ that synergizes with tumor-derived DNA to activate the STING pathway and drive repolarization toward an M1 anti-tumor phenotype. At the same time, LDHMP consumes excess H + , neutralizing the acidic milieu that normally suppresses immune function. This dual action-in situ reprogramming plus microenvironment remodeling-elicits robust, localized anti-tumor immunity without systemic toxicity. In orthotopic breast and pancreatic tumor models, Mip@MΦ treatment significantly inhibited tumor growth, reduced metastasis, and established durable immune memory. By combining a straightforward micropatch engineering strategy with insights from single-cell sequencing, our approach offers a scalable, safe, and highly effective platform for macrophage-based adoptive cell therapy.