| First Author | Kaczanowska S | Year | 2021 |
| Journal | Cell | Volume | 184 |
| Issue | 8 | Pages | 2033-2052.e21 |
| PubMed ID | 33765443 | Mgi Jnum | J:353210 |
| Mgi Id | MGI:6706314 | Doi | 10.1016/j.cell.2021.02.048 |
| Citation | Kaczanowska S, et al. (2021) Genetically engineered myeloid cells rebalance the core immune suppression program in metastasis. Cell 184(8):2033-2052.e21 |
| abstractText | Metastasis is the leading cause of cancer-related deaths, and greater knowledge of the metastatic microenvironment is necessary to effectively target this process. Microenvironmental changes occur at distant sites prior to clinically detectable metastatic disease; however, the key niche regulatory signals during metastatic progression remain poorly characterized. Here, we identify a core immune suppression gene signature in pre-metastatic niche formation that is expressed predominantly by myeloid cells. We target this immune suppression program by utilizing genetically engineered myeloid cells (GEMys) to deliver IL-12 to modulate the metastatic microenvironment. Our data demonstrate that IL12-GEMy treatment reverses immune suppression in the pre-metastatic niche by activating antigen presentation and T cell activation, resulting in reduced metastatic and primary tumor burden and improved survival of tumor-bearing mice. We demonstrate that IL12-GEMys can functionally modulate the core program of immune suppression in the pre-metastatic niche to successfully rebalance the dysregulated metastatic microenvironment in cancer. |
