人体免疫系统虽能清除癌细胞，但肿瘤微环境常会抑制免疫细胞功能，甚至重新编程肿瘤相关巨噬细胞以阻碍T细胞抗癌。为克服此屏障，阿得雷德大学赵春霞教授团队研发出一种新型系统，借由精准递送mRNA疗法，促使细胞产生可招募T细胞的CXCL9讯号，将受抑制的免疫细胞重新转化为抗癌同盟。

为防止免疫过度活化引发危险副作用，研究团队开发了表面修饰TREM2抗体的「智慧奈米粒子」，能精确锁定肿瘤内特定免疫抑制性巨噬细胞。此奈米粒子除了封装mRNA外，还搭载能刺激免疫途径的药物resiquimod，在体外实验中成功促使巨噬细胞大量表达CXCL9与活化标记NOS2，并显著下调免疫抑制讯号。

在侵袭性乳癌小鼠实验中，经三剂治疗后肿瘤生长显著趋缓，CXCL9浓度提高约四倍，且免疫抑制性巨噬细胞比例减少了63%。尽管结合免疫检查点抑制剂并未进一步缩小肿瘤，但增加了具有持久免疫潜力的T细胞浸润且无器官毒性，成功为标靶性mRNA癌症免疫疗法提供了关键的概念验证。

While the immune system can eliminate cancer cells, the tumor microenvironment often disarms immune defenses and reprograms tumor-associated macrophages to block T cell infiltration. To overcome this obstacle, a research team led by Professor Chunxia Zhao at the University of Adelaide developed a novel system that precisely delivers an mRNA therapy to induce CXCL9 production for T cell recruitment, successfully turning suppressive immune cells back into allies.

To avoid dangerous side effects from systemic immune hyperactivation, the researchers engineered 'smart' nanoparticles coated with TREM2 antibodies to selectively target immunosuppressive macrophages within the tumor. In addition to mRNA, these nanoparticles carry the immune-stimulating drug resiquimod, which in laboratory assays prompted macrophages to express high levels of CXCL9 and the activation marker NOS2 while significantly reducing immunosuppressive signals.

In mice with aggressive breast cancer, three doses of the nanoparticles markedly slowed tumor growth, quadrupled CXCL9 levels, and reduced immunosuppressive macrophages by 63 percent. Although combining this approach with immune checkpoint inhibitors did not further shrink tumor volume, it enriched T cells associated with long-term immune responses without causing adverse organ damage, establishing an encouraging proof-of-concept for targeted mRNA cancer immunotherapy.