当前位置：
X-MOL 学术
›
Immunology
›
论文详情
Our official English website, www.x-mol.net, welcomes your
feedback! (Note: you will need to create a separate account there.)
FEN1 inhibitor SC13 promotes CAR-T cells infiltration into solid tumours through cGAS–STING signalling pathway
Immunology ( IF 4.9 ) Pub Date : 2023-07-27 , DOI: 10.1111/imm.13681 Yunfei Dong 1 , Yuanyuan Wang 1 , Xuechen Yin 1 , Hongqiao Zhu 1 , Lingjie Liu 2 , Miaomiao Zhang 1 , Jiannan Chen 1 , Aying Wang 3 , Tinghui Huang 1 , Jianhua Hu 4 , Junqing Liang 5 , Zhigang Guo 1 , Lingfeng He 1
Immunology ( IF 4.9 ) Pub Date : 2023-07-27 , DOI: 10.1111/imm.13681 Yunfei Dong 1 , Yuanyuan Wang 1 , Xuechen Yin 1 , Hongqiao Zhu 1 , Lingjie Liu 2 , Miaomiao Zhang 1 , Jiannan Chen 1 , Aying Wang 3 , Tinghui Huang 1 , Jianhua Hu 4 , Junqing Liang 5 , Zhigang Guo 1 , Lingfeng He 1
Affiliation
|
It is well known that chimeric antigen receptor T-cell immunotherapy (CAR-T-cell immunotherapy) has excellent therapeutic effect in haematological tumours, but it still faces great challenges in solid tumours, including inefficient T-cell tumour infiltration and poor functional persistence. Flap structure-specific endonuclease 1 (FEN1), highly expressed in a variety of cancer cells, plays an important role in both DNA replication and repair. Previous studies have reported that FEN1 inhibition is an effective strategy for cancer treatment. Therefore, we hypothesized whether FEN1 inhibitors combined with CAR-T-cell immunotherapy would have a stronger killing effect on solid tumours. The results showed that low dose of FEN1 inhibitors SC13 could induce an increase of double-stranded broken DNA (dsDNA) in the cytoplasm. Cytosolic dsDNA can activate the cyclic GMP–AMP synthase–stimulator of interferon gene signalling pathway and increase the secretion of chemokines. In vivo, under the action of FEN1 inhibitor SC13, more chemokines were produced at solid tumour sites, which promoted the infiltration of CAR-T cells and improved anti-tumour immunity. These findings suggest that FEN1 inhibitors could enable CAR-T cells to overcome poor T-cell infiltration and improve the treatment of solid tumours.
中文翻译：
FEN1抑制剂SC13通过cGAS-STING信号通路促进CAR-T细胞浸润实体瘤
众所周知，嵌合抗原受体T细胞免疫疗法（CAR-T细胞免疫疗法）在血液肿瘤中具有优异的治疗效果，但在实体瘤中仍面临巨大挑战，包括T细胞肿瘤浸润效率低、功能持久性差等。Flap 结构特异性核酸内切酶 1 (FEN1) 在多种癌细胞中高表达，在 DNA 复制和修复中发挥着重要作用。先前的研究报告称，抑制 FEN1 是治疗癌症的有效策略。因此，我们推测FEN1抑制剂联合CAR-T细胞免疫治疗是否会对实体瘤产生更强的杀伤作用。结果表明，低剂量的FEN1抑制剂SC13可以诱导细胞质中双链断裂DNA（dsDNA）的增加。胞浆dsDNA可以激活干扰素基因信号通路的环GMP-AMP合成酶刺激剂并增加趋化因子的分泌。在体内，在FEN1抑制剂SC13的作用下，实体瘤部位产生更多的趋化因子，促进CAR-T细胞的浸润，提高抗肿瘤免疫力。这些发现表明，FEN1 抑制剂可以使 CAR-T 细胞克服 T 细胞浸润不良的问题，改善实体瘤的治疗。
更新日期：2023-07-27
中文翻译：
FEN1抑制剂SC13通过cGAS-STING信号通路促进CAR-T细胞浸润实体瘤
众所周知，嵌合抗原受体T细胞免疫疗法（CAR-T细胞免疫疗法）在血液肿瘤中具有优异的治疗效果，但在实体瘤中仍面临巨大挑战，包括T细胞肿瘤浸润效率低、功能持久性差等。Flap 结构特异性核酸内切酶 1 (FEN1) 在多种癌细胞中高表达，在 DNA 复制和修复中发挥着重要作用。先前的研究报告称，抑制 FEN1 是治疗癌症的有效策略。因此，我们推测FEN1抑制剂联合CAR-T细胞免疫治疗是否会对实体瘤产生更强的杀伤作用。结果表明，低剂量的FEN1抑制剂SC13可以诱导细胞质中双链断裂DNA（dsDNA）的增加。胞浆dsDNA可以激活干扰素基因信号通路的环GMP-AMP合成酶刺激剂并增加趋化因子的分泌。在体内，在FEN1抑制剂SC13的作用下，实体瘤部位产生更多的趋化因子，促进CAR-T细胞的浸润，提高抗肿瘤免疫力。这些发现表明，FEN1 抑制剂可以使 CAR-T 细胞克服 T 细胞浸润不良的问题，改善实体瘤的治疗。
京公网安备 11010802027423号