基于 DNA 超分子水凝胶的保护性 NK 细胞储库用于增强三阴性乳腺癌治疗
Protective NK Cell Reservoir Based on DNA Supramolecular Hydrogel for Enhanced Triple-Negative Breast Cancer Therapy.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Rhus Verniciflua Stokes Inhibits PD-1 Expression and Induces Anticancer Effects by Enhancing T Cell Function.
Rhus Verniciflua Stokes Inhibits PD-1 Expression and Induces Anticancer Effects by Enhancing T Cell Function.
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我们的研究结果表明,RVS 治疗通过降低 PD-1 表达增强 T 细胞对抗乳腺癌细胞的功能。这些结果提示,RVS 的成分可能成为癌症治疗中恢复耗竭 T 细胞的潜在候选物。
在过去十年中,漆树(Rhus verniciflua Stokes, RVS)的抗癌作用已在多项临床前或临床研究中被报道。然而,RVS 对免疫肿瘤学的影响,尤其是对 T 细胞功能特性及其表型的影响,仍不清楚。在此,我们计划研究 RVS 对免疫肿瘤学的影响,特别聚焦于其对 T 细胞的作用。
从乳腺癌患者中分离外周血单个核细胞(PBMCs),以获得CD3+ T细胞比例>85%的细胞因子诱导的杀伤细胞群体。通过将红色荧光蛋白(RFP)导入HLA-A02:01型匹配的乳腺癌细胞系(MCF7和MDA-MB-231),并使用流式细胞术分析结果,评估这些T细胞的抗癌活性。使用CTLA-4和PD-1等标志物,以及关键基因(IFN-γ、TNF-α和IL-2)的mRNA表达水平,评估RVS提取物对T细胞表型的影响。
RVS处理显著增强了T细胞对乳腺癌细胞的抗癌活性。具体而言,与对照组相比,经100 µg/mL RVS处理的T细胞对MCF-7细胞的细胞毒性增加了20.6%,对MDA-MB231细胞的细胞毒性增加了36.2%。此外,RVS处理导致T细胞上PD-1表达显著降低。
Over the last decade, the anticancer effects of Rhus verniciflua Stokes (RVS) have been reported in various preclinical or clinical studies. However, the effects of RVS on immuno-oncology, especially on the functional properties of T cells and their phenotypes, remain unclear. Here, we planned to investigate the impact of RVS on immuno-oncology, specifically focusing on its effects on T cells.
Peripheral blood mononuclear cells (PBMCs) from breast cancer patients were isolated to obtain cytokine-induced killer cell populations with >85% CD3+ T cells. The anticancer activity of these T cells was evaluated by introducing red fluorescent protein (RFP) into HLA-A02:01 type-matched breast cancer cell lines (MCF7 and MDA-MB-231) and analyzing the results using flow cytometry. The effect of RVS extracts on T cell phenotype was assessed using markers such as CTLA-4 and PD-1, as well as mRNA expression levels of key genes (IFN-γ, TNF-α, and IL-2).
RVS treatment significantly enhanced the anticancer activity of T cells against breast cancer cells. Specifically, T cells treated with 100 µg/mL of RVS showed a 20.6% increase in cytotoxicity against MCF-7 cells and a 36.2% increase against MDA-MB231 cells compared to the control. Additionally, RVS treatment led to a significant reduction in PD-1 expression on T cells.
Our findings demonstrate that RVS treatment enhances T cell function against breast cancer cells by reducing PD-1 expression. These results suggest that components of RVS may serve as potential candidates for restoring exhausted T cells in cancer therapy.
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