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:Dendritic cell-based immunotherapy modulates the systemic inflammatory profile in a 4T1 breast cancer model.
Dendritic cell-based immunotherapy modulates the systemic inflammatory profile in a 4T1 breast cancer model.
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基于 DC 的免疫治疗调节全身/腹腔炎症谱并减弱促肿瘤炎症。该策略可能为对常规治疗或基于 ICI 的治疗无应答的乳腺癌患者提供治疗获益,并支持其在转化研究中进一步评估。
乳腺癌仍是女性癌症相关死亡的主要原因,尤其是在治疗选择有限的晚期阶段。虽然免疫检查点抑制剂(ICIs)已改善了部分患者的结局,但许多患者无应答,凸显了对替代免疫治疗策略的需求。本研究在4T1小鼠乳腺癌模型中评估了基于树突状细胞(DC)的免疫疗法对肿瘤生长及腹腔髓系细胞炎症特征的影响。
采用骨髓来源的DC免疫疗法治疗荷4T1乳腺肿瘤的BALB/c小鼠。随时间监测肿瘤体积,并通过流式细胞术分析腹腔灌洗液中获得的CD14+细胞,检测细胞因子IL-12、IL-17和TNF-α以及转录因子RORγT和GATA3。
DC 为基础的免疫治疗与肿瘤体积减小的非显著趋势以及关键促炎细胞因子的显著抑制相关:IL-12(P < 0.0005)、IL-17(P < 0.0001)和 TNF-α(P < 0.0001)。与 Th17 和 Th2 分化相关的转录因子 RORγT 和 GATA3 的表达也下调(P < 0.0001)。这些免疫学效应在来自腹膜腔的 CD14 + 髓系细胞中观察到。
BALB/c mice bearing 4T1 breast tumors were treated with bone marrow-derived DC-based immunotherapy. Tumor volume was monitored over time, and CD14 + cells obtained from peritoneal lavage were analyzed by flow cytometry for the cytokines IL-12, IL-17, and TNF-α and the transcription factors RORγT and GATA3.
DC-based immunotherapy was associated with a non-significant trend toward reduced tumor volume and a marked suppression of key proinflammatory cytokines: IL-12 ( P < 0.0005), IL-17 ( P < 0.0001), and TNF-α ( P < 0.0001). Expression of the transcription factors RORγT and GATA3, associated with Th17 and Th2 differentiation, was also downregulated ( P < 0.0001). These immunological effects were observed in CD14 + myeloid cells from the peritoneal compartment.
DC-based immunotherapy modulates the systemic/peritoneal inflammatory profile and attenuates tumor-promoting inflammation. This strategy may offer therapeutic benefit for patients with breast cancer who are unresponsive to conventional or ICI-based treatments and supports its further evaluation in translational studies.
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