| First Author | Meng J | Year | 2022 |
| Journal | Cell Rep | Volume | 38 |
| Issue | 10 | Pages | 110492 |
| PubMed ID | 35263601 | Mgi Jnum | J:324844 |
| Mgi Id | MGI:7281955 | Doi | 10.1016/j.celrep.2022.110492 |
| Citation | Meng J, et al. (2022) Tumor-derived Jagged1 promotes cancer progression through immune evasion. Cell Rep 38(10):110492 |
| abstractText | 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 cells to inhibit T 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 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. |
