Type I Interferon Delivery by iPSC-Derived Myeloid Cells Elicits Antitumor Immunity via XCR1+ Dendritic Cells.
Type I Interferon Delivery by iPSC-Derived Myeloid Cells Elicits Antitumor Immunity via XCR1+ Dendritic Cells.
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DOI：
10.1016/j.celrep.2019.08.086
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发表时间：
2019-10
期刊：
影响因子：
8.8
通讯作者：
Nobuhiro Tsuchiya;Rong Zhang;T. Iwama;Norihiro Ueda;Tianyi Liu;Minako Tatsumi;Yutaka Sasaki;R. Shi
中科院分区：
文献类型：
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作者：
Nobuhiro Tsuchiya;Rong Zhang;T. Iwama;Norihiro Ueda;Tianyi Liu;Minako Tatsumi;Yutaka Sasaki;R. Shi
I型干扰素（IFN）在抗肿瘤免疫中起重要作用。我们通过基因工程诱导的多能干细胞（iPSC）衍生的增殖性髓样细胞（iPSC-pMCs）产生IFN-α产生细胞。局部施用产生IFN-α的iPSC-pMCs（IFN-α-iPSC-pMCs）改变肿瘤微环境并传播与I型IFN相关的分子特征。基因修饰的细胞积极影响宿主XCR 1+树突状细胞，以增强CD 8 +T细胞引发，导致CXCR 3依赖性和STING-IRF 3途径非依赖性全身肿瘤控制。IFN-α-iPSC-pMCs联合免疫检查点阻断的给药克服了对单一治疗方式的耐药性，并产生了持久的抗肿瘤免疫力。这些临床前数据表明，IFN-α-iPSC-pMCs可能构成对检查点阻断难治的癌症的有效免疫刺激剂。
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.