Scholarlink

<p>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 <i>Trmt61a</i>, the "writer" enzyme of tRNA N1-methyladenosine (m<sup>1</sup>A) modification, is highly expressed in proinflammatory macrophages in tumor microenvironment. We generated conditional knockout (KO) mice for <i>Trmt61a</i> and observed that <i>Trmt61a</i> deletion in macrophages significantly promoted tumor growth. Mechanistically, we identified that m<sup>1</sup>A maintains the translation of STING, enhances STING-TBK1-IFN-β signaling in macrophages and therefore suppresses tumor cell growth. We further generated <i>TRMT61A</i>-overexpressing human iPSC-derived CAR-macrophage and demonstrated that human <i>TRMT61A</i> effectively promoted antitumor CAR-macrophage therapy in vivo. Collectively, our findings reveal a novel regulatory mechanism of tRNA m<sup>1</sup>A modification in macrophages, highlighting the antitumor therapeutic potential of targeting tRNA m<sup>1</sup>A modification in macrophages.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

tRNA m1A modification orchestrates STING translation in macrophages to enhance antitumor immunity and CAR-macrophage immunotherapy

  • 期刊论文

  • 发表日期：

    2026年1月14日

查看全文
  • Xuefei Wang,
  • Xudong Wang,
  • Hao Li,
  • Shuyu Liu,
  • Yang Lu,
  • Huifang Chen,
  • Xueming Cai,
  • Siyu Su,
  • Bin Li,
  • Rujuan Liu,
  • Weiguo Hu,
  • Xiangjia Zhu,
  • Jin Zhang,
  • Youqiong Ye,
  • Hua-Bing Li

摘要

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 (m1A) 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 m1A 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 m1A modification in macrophages, highlighting the antitumor therapeutic potential of targeting tRNA m1A modification in macrophages.