RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:D-MT prompts the anti-tumor effect of oxaliplatin by inhibiting IDO expression in a mouse model of colon cancer.
D-MT prompts the anti-tumor effect of oxaliplatin by inhibiting IDO expression in a mouse model of colon cancer.
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结肠癌是消化系统最常见的恶性肿瘤之一。尽管化疗药物奥沙利铂已在临床上用于治疗结肠癌,但其治疗效果并不理想。已证实吲哚胺2,3-双加氧酶(IDO)是免疫应答中的一种肿瘤免疫抑制因子。在此,我们将一种IDO抑制剂D-MT(indoximod,1-甲基-D-色氨酸)与奥沙利铂联合用于治疗小鼠结肠癌。检测并记录了肿瘤组织中的T细胞浸润、脾脏中免疫细胞的比例以及小鼠的肿瘤生长和生存情况。结果表明,奥沙利铂与D-MT联合使用显著抑制了肿瘤生长并延长了荷瘤小鼠的生存期。更重要的是,联合治疗提高了荷瘤小鼠脾脏中CD4+ T、CD8+ T和NK细胞的比例,并促进了肿瘤组织中的T细胞浸润。本研究为临床结肠癌治疗提供了一种新的治疗策略,尤其是对于奥沙利铂耐药的患者。
Colon cancer is one of the most common malignant tumors in the digestive system. Although oxaliplatin, a chemotherapy drug, has been clinically used to treat colon cancer, its therapeutic effect is unsatisfactory. It has been proved that indoleamine dioxygenase 2,3 (IDO) is a tumor immunosuppressive factor for the immune response.
Herein, an IDO inhibitor, D-MT (indoximod, 1-Methyl-D-tryptophan), was combined with oxaliplatin to treat colon cancer in mice. T cell infiltration in tumor tissues, the ratios of immune cells in the spleens, and the tumor growth and survival of the mice were detected and recorded.
The results showed that the combination of oxaliplatin and D-MT significantly inhibited tumor growth and prolonged the survival of tumor-bearing mice. More importantly, the combination treatment increased the ratios of CD4 + T, CD8 + T and NK cells from the spleen in tumor-bearing mice, and prompted T cell infiltration in tumor tissues.
This study provided a new therapeutic strategy for colon cancer treatment in the clinic, especially for patients with oxaliplatin resistance.
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