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用源自分枝杆菌的 toll 样受体激动剂进行树突状细胞疫苗接种可增强抗肿瘤免疫力。

Dendritic cell vaccination with a toll-like receptor agonist derived from mycobacteria enhances anti-tumor immunity.

作者信息

Vo Manh-Cuong, Lee Hyun-Ju, Kim Jong-Seok, Hoang My-Dung, Choi Nu-Ri, Rhee Joon Haeng, Lakshmanan Vinoth-Kumar, Shin Sung-Jae, Lee Je-Jung

机构信息

Research Center for Cancer Immunotherapy, Chonnam National University Hwasun Hospital, Jeollanamdo, Republic of Korea.

Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Jeollanamdo, Republic of Korea.

出版信息

Oncotarget. 2015 Oct 20;6(32):33781-90. doi: 10.18632/oncotarget.5281.

Abstract

Dendritic cell (DC)-based vaccines are considered useful in cancer immunotherapy, and the interaction of DC and adjuvants is important in the design of the next generation vaccines. In this study, whether DC combined with Rv2299c derived from mycobacteria could improve anti-tumor immune responses in a colon cancer mouse model was evaluated. MC38 cell lines were injected subcutaneously to establish colon-cancer-bearing mice and the following four groups were evaluated: PBS control, tumor antigen (TA) loaded-DC, Rv2299c, and a combination of TA-loaded-DC and Rv2299c. The combination treatment with TA-loaded-DC and Rv2299c exhibited greater inhibition of tumor growth compared to other groups. These effects were associated with the reduction of suppressor cells, such as myeloid-derived suppressor cells and regulatory T cells, and the induction of effector cells, such as CD4+ T cells and CD8+ T cells, in spleen, and with the activation of cytotoxic T Lymphocytes and NK cells. These results suggest that TA-loaded-DC vaccination with Rv2299c derived from mycobacteria enhanced anti-tumor immunity in a mouse colon cancer model by inhibiting the generation of immune-suppressive cells and recovering numbers of effector cells, and demonstrated superior polarization of the Th1/Th2 balance in favor of the Th1 immune response.

摘要

基于树突状细胞(DC)的疫苗被认为在癌症免疫治疗中有用,并且DC与佐剂的相互作用在下一代疫苗的设计中很重要。在本研究中,评估了DC与源自分枝杆菌的Rv2299c联合使用是否能改善结肠癌小鼠模型中的抗肿瘤免疫反应。皮下注射MC38细胞系以建立荷结肠癌小鼠,并评估以下四组:PBS对照组、负载肿瘤抗原(TA)的DC、Rv2299c,以及负载TA的DC与Rv2299c的组合。与其他组相比,负载TA的DC与Rv2299c的联合治疗对肿瘤生长的抑制作用更大。这些效应与脾脏中抑制细胞(如髓系来源的抑制细胞和调节性T细胞)数量的减少以及效应细胞(如CD4+T细胞和CD8+T细胞)的诱导有关,也与细胞毒性T淋巴细胞和NK细胞的激活有关。这些结果表明,负载TA的DC疫苗与源自分枝杆菌的Rv2299c联合使用,通过抑制免疫抑制细胞的产生和恢复效应细胞数量,增强了小鼠结肠癌模型中的抗肿瘤免疫力,并显示出Th1/Th2平衡向有利于Th1免疫反应的方向的优越极化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52b4/4741802/0e78f6f08c52/oncotarget-06-33781-g001.jpg

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