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
抑制 CD24 表达通过改善荷黑色素瘤小鼠的抗肿瘤免疫反应增强内皮抑素的抗黑色素瘤效果
英文原题：Inhibition of CD24 Expression Enhances the Anti-Melanoma Effect of Endostatin by Ameliorating Anti-Tumor Immune Responses in Melanoma-Bearing Mice.
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Inhibition of CD24 Expression Enhances the Anti-Melanoma Effect of Endostatin by Ameliorating Anti-Tumor Immune Responses in Melanoma-Bearing Mice.
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研究概要
联合治疗重塑了免疫抑制性肿瘤微环境，增强了 M1 巨噬细胞和 T 淋巴细胞浸润，同时通过双重抑制 CD24 和 VEGF 抑制血管生成。将 CD24 抑制与抗血管生成治疗相结合可能为黑色素瘤提供一种新的治疗策略。
研究思路结论见上方概要
背景
黑色素瘤是一种高度侵袭性的皮肤癌，起源于转化的表皮黑素细胞，是全球增殖速度最快的恶性肿瘤之一。血管生成已被确定为黑色素瘤治疗的关键靶点，而内皮抑素已被证实可抑制内源性血管生成。然而，部分患者的治疗反应仍不理想。CD24作为一种抗吞噬信号，是肿瘤免疫治疗的潜在靶点。因此，在本研究中，我们探讨了联合抑制CD24与内皮抑素治疗对黑色素瘤的抗肿瘤效果。
方法
构建共表达质粒进行功能验证。采用荷黑色素瘤小鼠模型观察治疗过程中肿瘤大小的变化。通过Western blot、免疫荧光、TUNEL和流式细胞术检测蛋白表达、细胞凋亡、免疫细胞浸润及巨噬细胞亚群比例。
结果
共表达质粒显著抑制了细胞中CD24和VEGF的表达。联合治疗促进了肿瘤细胞凋亡并减少了血管生成。它还增加了肿瘤组织和脾脏中M1巨噬细胞、T淋巴细胞和NK细胞的浸润。基于质粒的联合治疗显著抑制了肿瘤生长，并延长了小鼠的生存时间。
展开英文摘要原文
MATERIALS AND METHODS
The co-expressed plasmid was constructed for functional verification. A melanoma-bearing mouse model was used to observe changes in tumor size during treatment. Protein expression, apoptosis, immune cell infiltration, and macrophage subset proportions were measured using Western blot, immunofluorescence, TUNEL, and flow cytometry assays.
RESULTS
The co-expressed plasmid significantly inhibited CD24 and VEGF expression in cells. The combination therapy promoted tumor cell apoptosis and decreased angiogenesis. It also increased infiltration of M1 macrophages, T lymphocytes, and NK cells in tumor tissue and the spleen. The combined plasmid-based therapy considerably suppressed tumor growth and lengthened the survival time of mice. DISCUSSION: The combination therapy remodeled the immunosuppressive tumor microenvironment, enhancing M1 macrophage and T lymphocyte infiltration while suppressing angiogenesis via dual inhibition of CD24 and VEGF.
CONCLUSION
Combining CD24 inhibition with antiangiogenic therapy could offer a novel therapeutic strategy for melanoma.
论文信息
- 作者
- Lei M、Liu Z、Lu F、Zu W、Li M、Wang M、Deng C、Fan M
- 单位
- Department of Immunology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan 453000, P.R. China.China
- 期刊
- Current cancer drug targets2026 Jan 12
- 原文标识
- PubMed 41572681 · DOI 10.2174/0115680096419727251121103534