| Literature DB >> 31577946 |
Nobuhiro Tsuchiya1, Rong Zhang2, Tatsuaki Iwama3, Norihiro Ueda4, Tianyi Liu5, Minako Tatsumi6, Yutaka Sasaki7, Ranmaru Shimoda8, Yuki Osako8, Yu Sawada9, Yosuke Kubo10, Azusa Miyashita10, Satoshi Fukushima10, Zhao Cheng11, Ryo Nakaki8, Keiyo Takubo12, Seiji Okada13, Shin Kaneko14, Hironobu Ihn10, Tsuneyasu Kaisho15, Yasuharu Nishimura16, Satoru Senju17, Itaru Endo9, Tetsuya Nakatsura3, Yasushi Uemura18.
Abstract
Type 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.Entities:
Keywords: CXCR3; PD-1; STING; XCR1; cancer immunotherapy; checkpoint blockade; cross-presentation; dendritic cells; induced pluripotent stem cells; type I interferon
Year: 2019 PMID： 31577946 DOI： 10.1016/j.celrep.2019.08.086
Source DB: PubMed Journal: Cell Rep Impact factor: 9.423