期刊
CELL
卷 184, 期 8, 页码 2033-+出版社
CELL PRESS
DOI: 10.1016/j.cell.2021.02.048
关键词
-
资金
- US National Institutes of Health [ZIA BC 011332, ZIA BC 011334]
- Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health, USA
By utilizing genetically engineered myeloid cells to deliver IL-12, immune suppression in the premetastatic niche can be reversed, resulting in improved survival and reduced metastatic and primary tumor burden in tumor-bearing mice.
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 premetastatic 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 ILI 2-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.
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