Type I Interferon Delivery by iPSC-Derived Myeloid Cells Elicits Antitumor Immunity via XCR1+ Dendritic Cells

Publication date: 1 October 2019Source: Cell Reports, Volume 29, Issue 1Author(s): Nobuhiro Tsuchiya, Rong Zhang, Tatsuaki Iwama, Norihiro Ueda, Tianyi Liu, Minako Tatsumi, Yutaka Sasaki, Ranmaru Shimoda, Yuki Osako, Yu Sawada, Yosuke Kubo, Azusa Miyashita, Satoshi Fukushima, Zhao Cheng, Ryo Nakaki, Keiyo Takubo, Seiji Okada, Shin Kaneko, Hironobu Ihn, Tsuneyasu KaishoSummaryType I interferons (IFNs) play important roles in antitumor immunity. We generated IFN-α-producing cells by genetically engineered 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.Graphical Abstract
Source: Cell Reports - Category: Cytology Source Type: research