@article{204196,
  keywords = {Humans, signal transduction, Macrophages, Immune Evasion, Tumor Microenvironment, Triple Negative Breast Neoplasms},
  author = {Jingjing Meng and Yi-Zhou Jiang and Shen Zhao and Yuwei Tao and Tengjiang Zhang and Xuxiang Wang and Yuan Zhang and Keyong Sun and Min Yuan and Jin Chen and Yong Wei and Xun Lan and Mo Chen and Charles David and Zhijie Chang and Xiaohuan Guo and Deng Pan and Meng Chen and Zhi-Ming Shao and Yibin Kang and Hanqiu Zheng},
  title = {Tumor-derived Jagged1 promotes cancer progression through immune evasion},
  abstract = {<p>Immune checkpoint inhibitor (ICI) therapy is generating remarkable responses in individuals with cancer, but only a small portion of individuals with breast cancer respond well. Here we report that tumor-derived Jagged1 is a key regulator of the tumor immune microenvironment. Jagged1 promotes tumorigenesis in multiple spontaneous mammary tumor models. Through Jagged1-induced Notch activation, tumor cells increase expression and secretion of multiple cytokines to help recruit macrophages into the tumor microenvironment. Educated macrophages crosstalk with tumor-infiltrating T\&nbsp;cells to inhibit T\&nbsp;cell proliferation and tumoricidal activity. In individuals with triple-negative breast cancer, a high expression level of Jagged1 correlates with increased macrophage infiltration and decreased T\&nbsp;cell activity. Co-administration of an ICI PD-1 antibody with a Notch inhibitor significantly inhibits tumor growth in breast cancer models. Our findings establish a distinct signaling cascade by which Jagged1 promotes adaptive immune evasion of tumor cells and provide several possible therapeutic targets.</p>
},
  year = {2022},
  journal = {Cell Rep},
  volume = {38},
  pages = {110492},
  month = {03/2022},
  issn = {2211-1247},
  doi = {10.1016/j.celrep.2022.110492},
  language = {eng},
}