CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:CD8+ T Cells Primed by Antigenic Peptide-Pulsed B Cells or Dendritic Cells Generate Similar Anti-Tumor Response.
CD8+ T Cells Primed by Antigenic Peptide-Pulsed B Cells or Dendritic Cells Generate Similar Anti-Tumor Response.
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基于负载肽的抗原呈递细胞(APC)的疫苗一直作为治疗癌症的一种治疗策略被研究。然而,总体而言,它们在临床试验中显示出有限的疗效。树突状细胞(DC)因其交叉呈递抗原的能力而一直是基于APC疫苗的主要选择。B细胞作为疫苗APC的研究较少。在此,我们比较了使用B细胞或DC进行肽特异性致敏后所产生的活化T细胞的表型和抗肿瘤活性。
从C57Bl/6小鼠中分离B细胞和DC,分别用或不用脂多糖(LPS)处理以促进成熟,然后负载或不负载SIINFEKL肽,用以致敏来自OT-1小鼠的CD8+ T细胞。随后分析活化T细胞的表型和抗肿瘤疗效。
我们报告,未成熟B细胞和未成熟DC均能够类似地激活抗原特异性CD8+ T细胞。然而,与LPS成熟的B细胞相比,LPS成熟的DC在体外产生了更强的CD8+ T细胞活化特征。未成熟B细胞、成熟DC和未成熟DC在将致敏的CD8+ T细胞过继转移至荷瘤小鼠后,均产生了相似的抗肿瘤反应。
总体而言,我们的数据表明,B细胞和DC均能够致敏CD8+ T细胞并产生抗肿瘤反应。鉴于与DC相比,B细胞相对更容易培养和扩增,我们的研究表明,在进一步验证后,B细胞可以进一步研究作为基于肽的人类癌症疫苗的APC。
Background: Peptide-loaded antigen-presenting cell (APC)-based vaccines have been under investigation as a therapeutic approach for treating cancer.
However, in general they have demonstrated limited efficacy in clinical trials. Dendritic cells (DCs) have been the primary choice for APC-based vaccines given their ability to cross-present antigens. B cells have been less studied as APCs for vaccines.
Here we compare the phenotype and anti-tumor activity of activated T cells that result from peptide-specific priming using either B cells or DCs. Methods: B cells and DCs were isolated from C57Bl/6 mice, and either treated or not treated with lipopolysaccharide (LPS) for maturation, and then either loaded or not loaded with SIINFEKL peptide to prime CD8+ T cells from OT-1 mice.
Activated T cells were then analyzed for their phenotype and anti-tumor efficacy. Results: We report that both immature B cells and immature DCs were similarly capable of activating antigen-specific CD8+ T cells.
However, LPS-matured DCs generated a stronger CD8+ T cell activation profile in vitro compared to LPS-matured B cells. Immature B cells, mature DCs and immature DCs all generated a similar anti-tumor response upon adoptive transfer of primed CD8+ T cells to tumor-bearing mice.
Conclusions: Collectively, our data suggests that B cells and DCs are each capable of priming CD8+ T cells and generating anti-tumor responses. Given that B cells are relatively easier to culture and expand compared to DCs, our study suggests that, following further validation, B cells could be further investigated as APCs for peptide-based human cancer vaccines.
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