Role of dendritic cell membrane microbubbles in the activation of T cells and the killing of colorectal cancer cells

Xu Han; Zhang Liang; Leng Xiaojing; Yan Shujin; Pang Hua

doi:10.13406/j.cnki.cyxb.003821

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Role of dendritic cell membrane microbubbles in the activation of T cells and the killing of colorectal cancer cells

Excellence in medical insights：special colum for tumor and immunotherapy | 更新时间：2025-10-22

- Role of dendritic cell membrane microbubbles in the activation of T cells and the killing of colorectal cancer cells
- Journal of Chongqing Medical University Vol. 50, Issue 6, Pages: 750-757(2025)
- 作者机构：
  
  1.重庆医科大学附属第一医院核医学科，重庆 400042
  2.重庆医科大学附属第一医院超声科，重庆 400042
  3.重庆医科大学附属第二医院超声科，重庆 400010
- 作者简介：
- 基金信息：
- DOI：10.13406/j.cnki.cyxb.003821
  CLC： R730.51
- Received：09 February 2025，
  
  Revised：2025-03-20，
  
  Accepted：31 March 2025，
  
  Published：28 June 2025
- 稿件说明：
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徐菡,张亮,冷小静,等.树突状细胞膜微泡在T细胞激活与结直肠癌细胞杀伤中的作用研究[J].重庆医科大学学报,2025,50(6):750-757.

Xu Han,Zhang Liang,Leng Xiaojing,et al.Role of dendritic cell membrane microbubbles in the activation of T cells and the killing of colorectal cancer cells[J].Journal of Chongqing Medical University,2025,50(6):750-757.
徐菡,张亮,冷小静,等.树突状细胞膜微泡在T细胞激活与结直肠癌细胞杀伤中的作用研究[J].重庆医科大学学报,2025,50(6):750-757. DOI： 10.13406/j.cnki.cyxb.003821.

Xu Han,Zhang Liang,Leng Xiaojing,et al.Role of dendritic cell membrane microbubbles in the activation of T cells and the killing of colorectal cancer cells[J].Journal of Chongqing Medical University,2025,50(6):750-757. DOI： 10.13406/j.cnki.cyxb.003821.

摘要

目的

设计并评估一种基于树突状细胞膜微泡（dendritic cell membrane-derived microbubbles，DCM@MBs）的疫苗策略，探索其在肿瘤免疫治疗中的应用潜力，特别是通过激活T细胞实现肿瘤细胞的免疫特异性杀伤。

方法

首先，通过肿瘤细胞膜蛋白提取和树突状细胞（dendritic cells，DCs）激活实验，确认肿瘤抗原可以有效刺激未成熟DCs的成熟。然后，利用成熟的树突状细胞膜和脂质混合制备DCM@MBs，并通过共聚焦显微镜（confocal laser scanning microscope，CLSM）和十二烷基硫酸钠-聚丙烯酰胺凝胶电泳（sodium dodecyl sulfate-polyacrylamide gel electrophoresis，SDS-PAGE）等方法对其形态、大小及蛋白质组成进行表征分析。最后，通过体外共培养实验评估DCM@MBs对T细胞的激活作用，以及其在特异性杀伤肿瘤细胞中的能力。

结果

在树突状细胞体外激活实验中，肿瘤细胞膜蛋白刺激后，25 μg/mL组未成熟DCs表面主要组织相容性复合体Ⅱ类分子（major histocompatibility complex class Ⅱ，MHC Ⅱ）的表达水平为（25.167±1.203）%，与对照组相比明显升高（

0.001）；DCM@MBs呈现出由红色细胞膜包裹形成的微泡，且分散均匀，大小约为1~5 μm。在体外共培养实验中，DCM@MBs组T细胞INF-γ的分泌量为（120.574±5.179） pg/mL，与对照组相比明显促进了CD8

T细胞的激活（

0.001

）

；且对CT26.WT肿瘤细胞的免疫特异性杀伤率为（30.737±0.216）%，是4T1小鼠乳腺癌细胞杀伤率（9.893±0.341）%的3.11倍。

结论

DCM@MBs策略在肿瘤免疫治疗中展现了明显潜力，能够有效激活T细胞并特异性杀伤肿瘤细胞，为肿瘤免疫治疗提供了新思路。

Abstract

Objective

To design and evaluate a cell membrane vaccine strategy based on dendritic cell membrane microbubbles （DCM@MBs），and to explore its potential application in tumor immunotherapy，especially the immune-specific killing of tumor cells through the activation of T cells.

Methods

At first，tumor cell membrane proteins were extracted and dendritic cells（DCs） were activated to confirm that tumor antigens could effectively stimulate the maturation of immature DCs. Mature DC membranes were then mixed with lipids to prepare DCM@MBs，which were characterized for morphology，size，and protein composition by confocal laser scanning microscopy and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Finally，

in vitro

co-culture experiments were conducted to assess the effect of DCM@MBs on the activation of T cells and their ability for specific killing of tumor cells.

Results

In the

in vitro

DC activation experiment，after stimulation with tumor cell membrane proteins，the 25 μg/mL group had a significant increase in the expression level of MHC class Ⅱ molecule（25.167%±1.203%） on the surface of immature DCs compared with the control group（

0.001），and DCM@MBs presented with microbubbles encapsulated by red cell membranes，with uniform dispersion and a size of 1-5 μm. In the

in vitro

co-culture experiment，the amount of INF-γ secreted by T cells was （120.574±5.179） pg/mL in the DCM@MBs group，significantly enhancing the activation of CD8

T cells compared with the control group（

0.001），and furthermore，the immune-specific killing rate against CT26.WT tumor cells was （30.737±0.216）%，which was 3.11 times that against 4T1 mouse breast cancer cells （9.893±0.341）% .

Conclusion

The DCM@MBs strategy proposed in this study shows significant potential in tumor immunotherapy and can effectively activate T cells and specifically kill and eliminate tumor cells，which provides new ideas for tumor immunotherapy.

关键词

Keywords

references

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