免疫检查点阻断通过扩增效应 CD8⁺ T 细胞克隆增强淋巴细胞清除性化疗诱导的抗肿瘤免疫
Immune Checkpoint Blockade Augments Lymphodepleting Chemotherapy-Induced Antitumor Immunity by Expanding Effector CD8+ T-cell Clones.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
抑制血红素加氧酶 1 可抑制葡萄膜黑色素瘤的生长、迁移和侵袭，并调节肿瘤浸润性 CD8+ T 细胞
英文原题：Inhibition of Heme Oxygenase 1 Suppresses Growth, Migration, and Invasion, and Regulates Tumor-Infiltrating CD8+ T Cells and in Uveal Melanoma.
查看英文原题
Inhibition of Heme Oxygenase 1 Suppresses Growth, Migration, and Invasion, and Regulates Tumor-Infiltrating CD8+ T Cells and in Uveal Melanoma.
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研究概要
这些结果表明，在 UM 中靶向 HO-1 具有作为独立靶向免疫治疗或辅助免疫治疗的潜力。
研究思路结论见上方概要
目的
转移性葡萄膜黑色素瘤（UM）治疗困难，亟需有效治疗方法。我们旨在探索血红素加氧酶1（HO-1）在UM中的作用，并为UM提供新的治疗策略。
方法
生物信息学用于分析HMOX1与UM及其他肿瘤中免疫的关系。使用CCK-8、Western blot、免疫荧光染色、伤口愈合和Transwell实验。使用小鼠皮下移植UM肿瘤模型验证治疗效果。
结果
在UM中，HMOX1的表达水平与免疫评分及多种免疫细胞的浸润水平强烈相关。ZnPP在体外可抑制UM细胞生长、促进细胞凋亡，并将细胞周期阻滞于G0/G1期。HO-1敲除可有效抑制UM细胞增殖。ZnPP在皮下肿瘤移植模型中有效抑制UM生长并促进CD8+ T细胞浸润。
展开英文摘要原文
PURPOSE
Metastatic uveal melanoma (UM) treatment is difficult, and effective treatments are urgently needed. We aimed to explore the role of heme oxygenase 1 (HO-1) in UM and provide new therapeutic strategies for UM.
METHODS
Bioinformatics was used to analyze the relationship between HMOX1 and immunity in UM and other tumors. Cell Counting Kit-8, Western blot, immunofluorescence staining, wound healing, and Transwell assays were used. A subcutaneous transplanted UM tumor model was used in mice to verify the therapeutic effect.
RESULTS
In UM, the expression level of HMOX1 was strongly correlated with the immune score and the infiltration level of various immune cells. ZnPP can inhibit the growth of UM cells, promote cell apoptosis, and block the cell cycle at G0/G1 phase in vitro. HO-1 knockout can effectively inhibit the proliferation of UM cells. ZnPP effectively inhibited the growth of UM and promoted the infiltration of CD8+ T cells in a subcutaneous tumor transplantation model.
CONCLUSIONS
These results indicate that targeting HO-1 in UM has the potential for independent targeted immunotherapy or adjuvant immunotherapy.
论文信息
- 作者
- Hou C、Wan Q、Xiao L、Xiao Q、Zhang M、Yan N
- 第一作者单位
- Research Laboratory of Macular Disease, West China Hospital, Sichuan University, Chengdu, China.China
- 通讯作者单位
- Research Laboratory of Ophthalmology, West China Hospital, Sichuan University, Chengdu, China.China
- 文献类型
- 非美国政府资助研究
- 期刊
- Investigative ophthalmology & visual science2024 Aug 1
- 原文标识
- PubMed 39186260 · DOI 10.1167/iovs.65.10.37
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