不适合移植的大 B 细胞淋巴瘤二线使用 axicabtagene ciloleucel：ALYCANTE 最终分析
Second-line axicabtagene ciloleucel in large B-cell lymphoma ineligible for transplantation: ALYCANTE final analysis.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
MicroRNA-146a 通过靶向程序性细胞死亡配体 1 抑制弥漫性大 B 细胞淋巴瘤的进展和免疫逃逸
英文原题：MicroRNA-146a Inhibits Progression and Immune Evasion in Diffuse Large B-cell Lymphomas by Targeting Programmed Cell Death Ligand 1.
查看英文原题
MicroRNA-146a Inhibits Progression and Immune Evasion in Diffuse Large B-cell Lymphomas by Targeting Programmed Cell Death Ligand 1.
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研究概要
我们的研究表明，miR-146a 通过靶向 PD-L1 增强抗肿瘤免疫，从而抑制 DLBCL 的进展。该 miRNA 在淋巴瘤中的治疗潜力非常值得期待。
研究思路结论见上方概要
背景
早期研究强调了miRNA146a在肿瘤抑制中的作用，表明其具有抑制弥漫性大B细胞淋巴瘤（DLBCL）进展的潜力。
目的
确定程序性死亡配体1（PD-L1）作为进一步研究的候选靶点，因为它在调节癌症免疫检查点中发挥关键作用，并与miRNA146a参与免疫调节和炎症反应相关。
方法
采用qPCR分析检测DLBCL细胞中miR-146a和PD-L1的表达。随后，用miR-146a模拟物或空白质粒处理DLBCL细胞（OCI-Ly-3和OCI-Ly-7）。为评估免疫逃逸，将DLBCL细胞与外周血单个核细胞、CD8+ T细胞或细胞因子诱导的杀伤细胞共培养。此外，对miR-146a的靶基因进行了预测和验证。
结果
与正常B细胞系（NCB）相比，DLBCL细胞中miR-146a水平显著降低。此外，miR-146a过表达显著降低了DLBCL的活力、侵袭和免疫逃逸，同时促进凋亡。我们的发现还证实miR-146a靶向PD-L1。最后，PD-L1上调显著逆转了miR-146a对DLBCL的肿瘤抑制作用。
展开英文摘要原文
BACKGROUND
Earlier studies have highlighted the involvement of miRNA146a in tumor suppression indicating its potential to inhibit the progression of diffuse large B-cell lymphoma (DLBCL).
OBJECTIVE
To identify programmed death-ligand 1 (PD-L1) as a candidate for further research, as it plays a key role in regulating immune checkpoints in cancer and is associated with the involvement of miRNA146a in immune regulation and the response to inflammation.
METHODS
The expression of miR-146a and PD-L1 in DLBCL cells was detected using qPCR analysis. Subsequently, DLBCL cells (OCI-Ly-3 and OCI-Ly-7) were treated with either the miR-146a mimic or a blank plasmid. To assess immune evasion, DLBCL cells were cocultured with peripheral blood mononuclear cells, CD8+ T cells, or cytokine-induced killer cells. Furthermore, the target gene of miR-146a was predicted and validated.
RESULTS
Compared to the normal B-cell line (NCB), the level of miR-146a was significantly lower in DLBCL cells. Additionally, overexpression of miR-146a significantly reduced DLBCL viability, invasion, and immune evasion while simultaneously promoting apoptosis. Our findings also confirmed that miR-146a targeted PD-L1. Finally, the upregulation of PD-L1 notably reversed the tumor suppressive effects of miR-146a on DLBCL.
CONCLUSION
Our study indicates that miR-146a inhibits the progression of DLBCL by enhancing antitumor immunity through the targeting of PD-L1. The therapeutic potential of this miRNA in lymphoma is highly desirable.
论文信息
- 作者
- Li Y、Wang X、Yang K
- 单位
- Department of Hematology, Hainan Cancer Hospital, Haikou City 570312, Hainan Province, China.China
- 期刊
- Iranian journal of immunology : IJI2025 Mar 30
- 原文标识
- PubMed 40130483 · DOI 10.22034/iji.2025.104027.2874