Type I Interferon Delivery by iPSC-Derived Myeloid Cells Elicits Antitumor Immunity Via XCR1 <sup>+</sup> Dendritic Cells
説明
Type I interferons (IFNs) play important roles in antitumor immunity. We generated IFN-α-producing cells by genetically engineering induced pluripotent stem cell (iPSC)-derived proliferating myeloid cells (iPSC-pMCs). Local administration of IFN-α-producing iPSC-pMCs (IFN-α-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-α-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-α-iPSC-pMCs might constitute effective immune-stimulating agents for cancer that are refractory to checkpoint blockade.
収録刊行物
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- SSRN Electronic Journal
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SSRN Electronic Journal 2019-01-01
Elsevier BV