First Author | Tsuchiya N | Year | 2019 |
Journal | Cell Rep | Volume | 29 |
Issue | 1 | Pages | 162-175.e9 |
PubMed ID | 31577946 | Mgi Jnum | J:286924 |
Mgi Id | MGI:6390639 | Doi | 10.1016/j.celrep.2019.08.086 |
Citation | Tsuchiya N, et al. (2019) Type I Interferon Delivery by iPSC-Derived Myeloid Cells Elicits Antitumor Immunity via XCR1(+) Dendritic Cells. Cell Rep 29(1):162-175.e9 |
abstractText | Type I interferons (IFNs) play important roles in antitumor immunity. We generated IFN-alpha-producing cells by genetically engineered induced pluripotent stem cell (iPSC)-derived proliferating myeloid cells (iPSC-pMCs). Local administration of IFN-alpha-producing iPSC-pMCs (IFN-alpha-iPSC-pMCs) alters the tumor microenvironment and propagates the molecular signature associated with type I IFN. The gene-modified cell actively influences host XCR1(+) dendritic cells to enhance CD8(+) T cell priming, resulting in CXCR3-dependent and STING-IRF3 pathway-independent systemic tumor control. Administration of IFN-alpha-iPSC-pMCs in combination with immune checkpoint blockade overcomes resistance to single-treatment modalities and generates long-lasting antitumor immunity. These preclinical data suggest that IFN-alpha-iPSC-pMCs might constitute effective immune-stimulating agents for cancer that are refractory to checkpoint blockade. |