干扰素基因刺激剂
刺
先天免疫系统
兴奋剂
癌症免疫疗法
细胞生物学
干扰素
免疫疗法
免疫系统
体内
体外
化学
生物
癌症研究
作者
Rebekah Watkins-Schulz,Cole J. Batty,Rebeca T. Stiepel,Megan E. Schmidt,Adam M Sandor,Wei-Chun Chou,Kathryn M. Moore,Eric M. Bachelder,Jenny P-Y Ting
标识
DOI:10.1021/acs.molpharmaceut.2c00207
摘要
Natural killer (NK) cells are an important member of the innate immune system and can participate in direct tumor cell killing in response to immunotherapies. One class of immunotherapy is stimulator of interferon gene (STING) agonists, which result in a robust type I interferon (IFN-I) response. Most mechanistic studies involving STING have focused on macrophages and T cells. Nevertheless, NK cells are also activated by IFN-I, but the effect of STING activation on NK cells remains to be adequately investigated. We show that both direct treatment with soluble STING agonist cyclic di-guanosine monophosphate-adenosine monophosphate (cGAMP) and indirect treatment with cGAMP encapsulated in microparticles (MPs) result in NK cell activation in vitro, although the former requires 100× more cGAMP than the latter. Additionally, direct activation with cGAMP leads to NK cell death. Indirect activation with cGAMP MPs does not result in NK cell death but rather cell activation and cell killing in vitro. In vivo, treatment with soluble cGAMP and cGAMP MPs both cause short-term activation, whereas only cGAMP MP treatment produces long-term changes in NK cell activation markers. Thus, this work indicates that treatment with an encapsulated STING agonist activates NK cells more efficiently than that with soluble cGAMP. In both the in vitro and in vivo systems, the MP delivery system results in more robust effects at a greatly reduced dosage. These results have potential applications in aiding the improvement of cancer immunotherapies.
科研通智能强力驱动
Strongly Powered by AbleSci AI