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巨噬细胞来源的树突状细胞增强头颈部鳞状细胞癌小鼠模型的抗肿瘤免疫

英文原题:Macrophage-derived dendritic cells enhance antitumor immunity in a mouse model of head and neck squamous cell carcinoma.

查看英文原题

Macrophage-derived dendritic cells enhance antitumor immunity in a mouse model of head and neck squamous cell carcinoma.

PubMed 2025/04/26(内容时间) Clin Transl Oncol Q3 · IF 2.7(JCR 2025)

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研究概要

BMΦDCs 是 HNSCC 的一种有前景的免疫治疗策略,表现出优越的抗肿瘤疗效、增强的免疫应答和良好的生物安全性。这些发现凸显了 BMΦDCs 在推进肿瘤免疫治疗方面的潜力。

研究思路结论见上方概要

本研究探讨骨髓巨噬细胞来源的树突状细胞(BMΦDCs)在增强抗头颈部鳞状细胞癌(HNSCC)抗肿瘤免疫中的治疗潜力,重点关注其在抑制肿瘤生长、减少转移和调节肿瘤微环境方面的作用。

BMΦDCs通过用巨噬细胞集落刺激因子(M-CSF)培养骨髓细胞,随后用粒细胞-巨噬细胞集落刺激因子(GM-CSF)和白细胞介素-4(IL-4)培养而生成。MTCQ-1肿瘤裂解物用于抗原负载。使用流式细胞术分析BMΦDCs的表型特征。在免疫健全的C57BL/6小鼠的皮下和肺转移模型中评估体内抗肿瘤疗效。监测肿瘤生长,并收集肿瘤组织,使用苏木精和伊红(H&E)、Masson三色染色和抗CD8染色进行组织学分析。

BMΦDCs 相比传统 BMDCs 表现出更高的成熟标志物表达(CD40、CD86)。在皮下肿瘤模型中,BMΦDCs 显著抑制肿瘤生长并增强细胞毒性 T 淋巴细胞(CTL)活性。在肺转移模型中,BMΦDCs 有效减轻转移负荷。组织学分析显示,BMΦDC 治疗小鼠中 CD8+ T 细胞浸润增加、肿瘤纤维化减少。未观察到明显毒性或器官损伤。

展开英文摘要原文

This study investigates the therapeutic potential of bone marrow macrophages-derived dendritic cells (BMΦDCs) in enhancing antitumor immunity against head and neck squamous cell carcinoma (HNSCC), focusing on their effects in inhibiting tumor growth, reducing metastasis, and modulating the tumor microenvironment.

BMΦDCs were generated by culturing bone marrow cells with macrophage colony-stimulating factor (M-CSF) followed by granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4). MTCQ-1 tumor lysates were used for antigen loading. The phenotypic characteristics of BMΦDCs were analyzed using flow cytometry. In vivo antitumor efficacy was assessed in subcutaneous and lung metastasis models in immunocompetent C57BL/6 mice. Tumor growth was monitored, and tumor tissues were collected for histological analysis using hematoxylin and eosin (H&E), Masson's trichrome, and anti-CD8 staining.

BMΦDCs displayed higher maturation marker expression (CD40, CD86) compared to traditional BMDCs. In the subcutaneous tumor model, BMΦDCs significantly inhibited tumor growth and enhanced cytotoxic T lymphocyte (CTL) activity. In the lung metastasis model, BMΦDCs effectively reduced metastatic burden. Histological analysis revealed increased CD8 + T cell infiltration and reduced tumor fibrosis in BMΦDC-treated mice. No significant toxicity or organ damage was observed.

BMΦDCs are a promising immunotherapeutic approach for HNSCC, demonstrating superior antitumor efficacy, enhanced immune responses, and excellent biosafety. These findings highlight the potential of BMΦDCs in advancing cancer immunotherapy.

论文信息

作者
Xie C、Wei F、Liu T、Li X、Chen K、Wen W、Sun W
第一作者单位
Department of Otolaryngology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510655, Guangdong, China.China
通讯作者单位
Department of Otolaryngology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, Guangdong, China. sunwei26@mail.sysu.edu.cn.China
期刊
Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico2025 Oct
原文标识
PubMed 40285810 · DOI 10.1007/s12094-025-03889-y