肿瘤细胞治疗研究
英文原题：CAR T cells, CAR NK cells, and CAR macrophages exhibit distinct traits in glioma models but are similarly enhanced when combined with cytokines.
嵌合抗原受体 (CAR) T 细胞疗法是一种有前景的抗癌免疫疗法。
嵌合抗原受体（CAR）T 细胞疗法是一种有前景的抗癌免疫疗法。尽管对其他细胞类型的兴趣日益增长，但在具有挑战性的实体瘤情境下，对 CAR 免疫效应细胞的比较仍属空白。在此，我们比较了表达小鼠和人 NKG2D-CAR 的 T 细胞、自然杀伤（NK）细胞和巨噬细胞针对胶质母细胞瘤——最具侵袭性的原发性脑肿瘤——的作用。在体外，我们显示 T 细胞的肿瘤杀伤依赖 CAR，而 NK 细胞的固有细胞毒性超越了 CAR 依赖性，CAR 巨噬细胞则在共培养实验中减少胶质瘤细胞。在原位免疫健全胶质瘤小鼠模型中，全身给药的 CAR T 细胞在肿瘤中表现出更优的蓄积，且每种免疫细胞类型均诱导肿瘤微环境发生不同的改变。在所有这些 CAR 免疫效应细胞中，共表达促炎细胞因子可显著增强原本较低的治疗效力，这凸显了采用多方面细胞工程策略以克服免疫抑制性实体瘤微环境的必要性。
Chimeric antigen receptor (CAR) T cell therapy is a promising immunotherapy against cancer. Although there is a growing interest in other cell types, a comparison of CAR immune effector cells in challenging solid tumor contexts is lacking. Here, we compare mouse and human NKG2D-CAR-expressing T cells, natural killer (NK) cells, and macrophages against glioblastoma, the most aggressive primary brain tumor. In vitro we show that T cell cancer killing is CAR dependent, whereas intrinsic cytotoxicity overrules CAR dependence for NK cells, and CAR macrophages reduce glioma cells in co-culture assays. In orthotopic immunocompetent glioma mouse models, systemically administered CAR T cells demonstrate superior accumulation in the tumor, and each immune cell type induces distinct changes in the tumor microenvironment. An otherwise low therapeutic efficacy is significantly enhanced by co-expression of pro-inflammatory cytokines in all CAR immune effector cells, underscoring the necessity for multifaceted cell engineering strategies to overcome the immunosuppressive solid tumor microenvironment.
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