Scholarlink

<p>Natural killer (NK) cells and T cells need to infiltrate solid tumors to eradicate them. Here we show programmable mechanisms that can mobilize NK and T cells to solid tumors using metabolite-sensing receptors. In vivo and in vitro CRISPR activation screens using NK-92 cells identified <i>GPR183</i>, <i>GPR84</i>, <i>GPR34</i> and <i>GPR18</i> as top enhancers of infiltration and chemotaxis to breast and ovarian cancers. While endogenously expressed in restricted cellular contexts, expressing these receptors in NK and T cells drives migration to factors released by cancer cells and alters the NK cell transcriptome in a ligand-dependent manner. Expressing GPR183 in NK, chimeric antigen receptor (CAR) NK and CAR T cells increased tumor infiltration and control. Likewise, expressing GPR183 in mouse T cells increased tumor eradication in immunocompetent mice. These data show that metabolite sensing can be rewired to obtain biochemically guided spatially targeted cells, creating new possibilities for therapeutic intervention.</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

Engineering NK and T cells with metabolite-sensing receptors to target solid tumors

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月23日

查看全文
  • Young-Min Kim,
  • Min K. Tsai,
  • Chang Sun,
  • Olivia Laveroni,
  • Reece Villarin Akana,
  • Kristen Frombach,
  • Livnat Jerby

摘要

Natural killer (NK) cells and T cells need to infiltrate solid tumors to eradicate them. Here we show programmable mechanisms that can mobilize NK and T cells to solid tumors using metabolite-sensing receptors. In vivo and in vitro CRISPR activation screens using NK-92 cells identified GPR183, GPR84, GPR34 and GPR18 as top enhancers of infiltration and chemotaxis to breast and ovarian cancers. While endogenously expressed in restricted cellular contexts, expressing these receptors in NK and T cells drives migration to factors released by cancer cells and alters the NK cell transcriptome in a ligand-dependent manner. Expressing GPR183 in NK, chimeric antigen receptor (CAR) NK and CAR T cells increased tumor infiltration and control. Likewise, expressing GPR183 in mouse T cells increased tumor eradication in immunocompetent mice. These data show that metabolite sensing can be rewired to obtain biochemically guided spatially targeted cells, creating new possibilities for therapeutic intervention.