血红素氧化酶1抑制剂抑制葡萄膜黑色素瘤的生长、迁移和侵袭，并调节肿瘤浸润的CD8+ T 细胞
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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影响因子:4.7
分区:医学2区 / 眼科学2区
发表日期:2024 Aug 01
作者:
Chen Hou, Qi Wan, Lirong Xiao, Qing Xiao, Meixia Zhang, Naihong Yan
DOI:
10.1167/iovs.65.10.37
摘要
转移性葡萄膜黑色素瘤（UM）治疗困难，亟需有效的治疗方法。本研究旨在探索血红素氧化酶1（HO-1）在UM中的作用，并提供新的治疗策略。采用生物信息学分析HMOX1与UM及其他肿瘤免疫的关系。实验方法包括细胞计数试剂盒-8（CCK-8）、Western印迹、免疫荧光染色、伤口愈合和Transwell迁移实验。使用小鼠皮下移植UM肿瘤模型验证治疗效果。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密切相关。ZnPP可抑制UM细胞的生长，促进细胞凋亡，并阻滞G0/G1期细胞周期。在体外，HO-1敲除能有效抑制UM细胞增殖。ZnPP在小鼠皮下肿瘤移植模型中有效抑制肿瘤生长，并促进CD8+ T细胞的浸润。这些结果表明，靶向HO-1在UM中具有潜在的独立靶向免疫治疗或辅助免疫治疗的可能性。
Abstract
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.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.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.These results indicate that targeting HO-1 in UM has the potential for independent targeted immunotherapy or adjuvant immunotherapy.