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:Enhanced effect of radiofrequency ablation on HCC by siRNA-PD-L1-endostatin Co-expression plasmid delivered.
Enhanced effect of radiofrequency ablation on HCC by siRNA-PD-L1-endostatin Co-expression plasmid delivered.
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肝细胞癌(HCC)因高死亡率和有限的治疗选择而构成重大临床挑战。射频消融(RFA)是常用方法,但受限于肿瘤复发。本研究探讨将RFA与携带siRNA-PD-L1和内皮抑素的减毒沙门氏菌联合使用以增强HCC治疗的潜力。本研究采用H22皮下肿瘤小鼠模型,将动物分为五组,分别接受空白对照、空白沙门氏菌质粒、单独RFA、siRNA-PD-L1-内皮抑素或RFA与siRNA-PD-L1-内皮抑素联合治疗。联合治疗显著减少了RFA后肿瘤组织中的肿瘤生长、血管生成以及PD-L1/VEGF表达。此外,它还诱导了肿瘤细胞凋亡,抑制了增殖和迁移,并增加了肿瘤内T淋巴细胞、颗粒酶B+ T细胞和CD86+巨噬细胞的浸润。脾脏中T细胞和NK细胞群体也显著增加。总之,将RFA与由减毒沙门氏菌递送的siRNA-PD-L1-内皮抑素联合使用可协同增强抗肿瘤效果,增强抗肿瘤免疫应答,并提高RFA对HCC的疗效。
Hepatocellular carcinoma (HCC) poses a significant clinical challenge due to high mortality and limited treatment options. Radiofrequency ablation (RFA) is commonly used but can be limited by tumor recurrence.
This study explores the potential of combining RFA with an attenuated Salmonella strain carrying siRNA-PD-L1 and endostatin to enhance HCC treatment. In this study, an H22 subcutaneous tumor mouse model was used, with animals divided into five groups for treatment with a blank control, a blank Salmonella plasmid, RFA alone, siRNA-PD-L1-endostatin, or a combination of RFA and siRNA-PD-L1-endostatin. The combination therapy significantly reduced tumor growth, angiogenesis, and PD-L1/VEGF expression in tumor tissues post-RFA.
Additionally, it induced tumor cell apoptosis, inhibited proliferation and migration, and increased the infiltration of T lymphocytes, granzyme B + T cells, and CD86 + macrophages within tumors. There was also a notable rise in T and NK cell populations in the spleen.
In conclusion, combining RFA with siRNA-PD-L1-endostatin delivered by attenuated Salmonella synergistically enhances anti-tumor effects, boosts the anti-tumor immune response, and improves RFA efficacy for HCC.
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