Division of Stem Cell Medicine, Graduate School of Medicine, Kobe University, Kobe, Hyogo, Japan; Division of Advanced Medical Science, Graduate School of Science, Technology and Innovation, Kobe University, Kobe, Hyogo, Japan; Division of Plastic Surgery, Graduate School of Medicine, Kobe University, Kobe, Hyogo, Japan.
Division of Stem Cell Medicine, Graduate School of Medicine, Kobe University, Kobe, Hyogo, Japan; Division of Advanced Medical Science, Graduate School of Science, Technology and Innovation, Kobe University, Kobe, Hyogo, Japan; Center for Human Resource Development for Regenerative Medicine, Kobe University Hospital, Kobe, Hyogo, Japan.
Stem Cell Reports. 2023 Apr 11;18(4):853-868. doi: 10.1016/j.stemcr.2023.02.010. Epub 2023 Mar 23.
For a long time, ex vivo-expanded peripheral-blood-derived γδT cell (PBγδT)-based immunotherapy has been attractive, and clinical trials have been undertaken. However, the difficulty in expanding cytotoxic γδT cells to an adequate number has been a major limitation to the efficacy of treatment in most cases. We successfully re-generated γδT cells from γδT cell-derived human induced pluripotent stem cells (iPSCs). The iPSC-derived γδT cells (iγδTs) killed several cancer types in a major histocompatibility complex (MHC)-unrestricted manner. Single-cell RNA sequencing (scRNA-seq) revealed that the iγδTs were identical to a minor subset of PBγδTs. Compared with a major subset of PBγδTs, the iγδTs showed a distinctive gene expression pattern: lower CD2, CD5, and antigen-presenting genes; higher CD7, KIT, and natural killer (NK) cell markers. The iγδTs expressed granzyme B and perforin but not interferon gamma (IFNγ). Our data provide a new source for γδT cell-based immunotherapy without quantitative limitation.
长期以来，体外扩增外周血源性 γδT 细胞（PBγδT）的免疫疗法一直很有吸引力，并已开展了临床试验。然而，在大多数情况下，将细胞毒性 γδT 细胞扩增到足够数量一直是治疗效果的主要限制因素。我们成功地从 γδT 细胞衍生的人诱导多能干细胞（iPSC）中重新生成 γδT 细胞。iPSC 衍生的 γδT 细胞（iγδT）以主要组织相容性复合体（MHC）非限制性方式杀伤多种癌症类型。单细胞 RNA 测序（scRNA-seq）显示，iγδT 与 PBγδT 的一小部分亚群相同。与 PBγδT 的主要亚群相比，iγδT 表现出独特的基因表达模式：CD2、CD5 和抗原呈递基因较低；CD7、KIT 和自然杀伤（NK）细胞标志物较高。iγδT 表达颗粒酶 B 和穿孔素，但不表达干扰素 γ（IFNγ）。我们的数据为基于 γδT 细胞的免疫疗法提供了一种新的来源，而没有定量限制。
