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树突状细胞免疫疗法在成熟过程中通过脂多糖提高了其抗肿瘤作用。

Dendritic cell immunotherapy has its antitumor action improved by the LPS in the maturation process.

作者信息

Lopes Angela Maria Moed, Vieira Jéssica Ferreira, da Silva Saulo Fernando Moreira, Murta Eddie Fernando Candido, Michelin Márcia Antoniazi

机构信息

Research Institute of Oncology (IPON), Federal University of Triângulo Mineiro (UFTM), Rua Vigário Carlos 100, Abadia, Uberaba, Minas Gerais, 38025-350, Brazil.

Discipline of Gynecology and Obstetrics, Federal University of Triângulo Mineiro (UFTM), Uberaba, MG, Brazil.

出版信息

Clin Transl Oncol. 2025 Feb 20. doi: 10.1007/s12094-025-03858-5.

Abstract

Immunotherapy with dendritic cells (DCs) in cancer patients aims to activate the immune response to eliminate neoplastic cells. The present study aimed to investigate lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells in investigating antitumor immune response in experimental breast cancer. For this, we submitted bone marrow pluripotent cells of Balb/c mice differentiated by GM-CSF and IL-4 to maturation with TNF-α and tumor lysate (DCs protocol) or with TNF-α, LPS, and tumor lysate (LPS/DCs protocol). Both immunotherapies were tested in 4T1 breast cancer to evaluate their impact on splenic and tumor microenvironment. We observed that DCs and LPS/DCs reduce the tumor growth rate (p < 0.0001). Besides, the LPS/DCs vaccine shows higher splenic and intratumoral T helper lymphocytes (p < 0.001). Both vaccines increased the production of IFN-γ in the tumor microenvironment (p < 0.0001). The LPS/DCs induced lower Treg lymphocytes and macrophages in the tumor microenvironment (p < 0.0001). The results allow us to conclude that bone marrow-derived dendritic cells stimulated with LPS have been shown to reduce tumor growth rate efficiently and could be better immunotherapy in breast cancer by reducing immunosuppressive cells and increasing antitumoral immune cells in the tumor microenvironment.

摘要

癌症患者的树突状细胞(DC)免疫疗法旨在激活免疫反应以消除肿瘤细胞。本研究旨在研究脂多糖(LPS)刺激的骨髓来源树突状细胞在实验性乳腺癌中的抗肿瘤免疫反应。为此,我们将经GM-CSF和IL-4分化的Balb/c小鼠骨髓多能细胞用TNF-α和肿瘤裂解物(DC方案)或用TNF-α、LPS和肿瘤裂解物(LPS/DC方案)进行成熟处理。两种免疫疗法均在4T1乳腺癌中进行测试,以评估它们对脾脏和肿瘤微环境的影响。我们观察到DC和LPS/DC降低了肿瘤生长速率(p < 0.0001)。此外,LPS/DC疫苗显示出更高的脾脏和肿瘤内辅助性T淋巴细胞(p < 0.001)。两种疫苗均增加了肿瘤微环境中IFN-γ的产生(p < 0.0001)。LPS/DC在肿瘤微环境中诱导产生的调节性T淋巴细胞和巨噬细胞较少(p < 0.0001)。结果使我们得出结论,LPS刺激的骨髓来源树突状细胞已被证明能有效降低肿瘤生长速率,并且通过减少免疫抑制细胞和增加肿瘤微环境中的抗肿瘤免疫细胞,可能成为乳腺癌更好的免疫疗法。

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