tRNA m1A 修饰在巨噬细胞中调控 STING 翻译，以增强抗肿瘤免疫及 CAR-巨噬细胞免疫治疗

Tumor-associated macrophages (TAMs) play crucial roles in tumor progression.

However, the mechanisms underlying the posttranscriptional regulation of TAMs remain largely unknown.

Here, we demonstrated that Trmt61a, the "writer" enzyme of tRNA N1-methyladenosine (m 1 A) modification, is highly expressed in proinflammatory macrophages in tumor microenvironment.

We generated conditional knockout (KO) mice for Trmt61a and observed that Trmt61a deletion in macrophages significantly promoted tumor growth.

Mechanistically, we identified that m 1 A maintains the translation of STING, enhances STING-TBK1-IFN-β signaling in macrophages and therefore suppresses tumor cell growth.

We further generated TRMT61A-overexpressing human iPSC-derived CAR-macrophage and demonstrated that human TRMT61A effectively promoted antitumor CAR-macrophage therapy in vivo. Collectively, our findings reveal a novel regulatory mechanism of tRNA m 1 A modification in macrophages, highlighting the antitumor therapeutic potential of targeting tRNA m 1 A modification in macrophages.