CAR-T（CAR-T）细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T（CAR-T）细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
经工程化改造分泌 IFNκ 的 CAR-T 细胞通过 IFNAR/STAT1/ACSL4 轴诱导肿瘤铁死亡
英文原题：CAR T Cells Engineered to Secrete IFNκ Induce Tumor Ferroptosis via an IFNAR/STAT1/ACSL4 Axis.
查看英文原题
CAR T Cells Engineered to Secrete IFNκ Induce Tumor Ferroptosis via an IFNAR/STAT1/ACSL4 Axis.
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中文摘要
铁死亡是一种铁依赖性的细胞死亡形式，影响癌症免疫。铁死亡的治疗性调控被认为是增强其他癌症疗法疗效的潜在策略，包括CAR-T 细胞疗法等免疫疗法。在本研究中，我们证明IFN影响铁死亡的诱导。IFN可增强肿瘤细胞对小分子化合物erastin和多不饱和脂肪酸花生四烯酸诱导的铁死亡的敏感性。在机制上，IFN与花生四烯酸联合通过IFNAR/STAT1/ACSL4轴诱导免疫原性肿瘤铁死亡。此外，经工程化表达IFN的CAR-T 细胞在体外和体内均显示出对H460细胞（抗原阳性）和H322细胞（抗原阴性）增强的抗肿瘤效率。我们得出结论，IFN是一种潜在的细胞因子，可通过诱导肿瘤铁死亡来增强CAR-T 细胞的抗肿瘤功能。
展开英文摘要原文
Ferroptosis is an iron-dependent form of cell death that influences cancer immunity. Therapeutic modulation of ferroptosis is considered a potential strategy to enhance the efficacy of other cancer therapies, including immunotherapies such as chimeric antigen receptor (CAR) T-cell therapy. In this study, we demonstrated that IFN influenced the induction of ferroptosis. IFN could enhance the sensitivity of tumor cells to ferroptosis induced by the small molecule compound erastin and the polyunsaturated fatty acid arachidonic acid.
Mechanistically, IFN in combination with arachidonic acid induced immunogenic tumor ferroptosis via an IFNAR/STAT1/ACSL4 axis.
Moreover, CAR T cells engineered to express IFN showed increased antitumor efficiency against H460 cells (antigen positive) and H322 cells (antigen-negative) both in vitro and in vivo.
We conclude that IFN is a potential cytokine that could be harnessed to enhance the antitumor function of CAR T cells by inducing tumor ferroptosis.
论文信息
- 作者
- Gao Y、Liu S、Huang Y、Wang H、Zhao Y、Cui X、Peng Y、Li F
- 单位
- Biotherapy Center and Cancer Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.China
- 文献类型
- 非美国政府资助研究
- 期刊
- Cancer immunology research2024 Dec 3
- 原文标识
- PubMed 39189923 · DOI 10.1158/2326-6066.CIR-24-0130
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