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首页> 外文期刊>Cell cycle >Brave little world: spheroids as an in vitro model to study tumor-immune-cell interactions.
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Brave little world: spheroids as an in vitro model to study tumor-immune-cell interactions.

机译:勇敢的小世界:球体作为研究肿瘤-免疫细胞相互作用的体外模型。

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摘要

Multicellular tumor spheroids (MCTS) are a well-established 3-D in vitro model system that reflects the pathophysiological in vivo situation in tumor microregions and of avascular micrometastatic sites. Because monocytes and other immune cells infiltrate into MCTS of different origin, such spheroid cocultures are a valuable, still underestimated tool to systematically study heterologous interactions between tumor and immune cells. The present article gives a brief overview on work that has been published on tumor-immune cell interactions in MCTS and also summarizes mechanisms of immune suppression in the tumor milieu focussing on myeloid cells. Using the coculture model, we recently demonstrated that tumor-derived lactic acid is a potent modulator of human monocyte as lactic acid inhibited the differentiation of monocytes (MO) into dendritic cells (DC) and also impaired antigen presentation. We show herein, that the capacity of various tumor cells in MCTS to secrete lactic acid differs up to tenfold, suggesting that this capacity is dependent on the tumor cell type. It is further demonstrated that lactic acid disturbs the migration of MO into MCTS as infiltration could be increased by blocking lactic acid production. We therefore discuss lactic acid which accumulates in many tumors and tumor microregions as a potent immune suppressor for MO/DC in the tumor milieu and conclude that these data are highly relevant for adoptive immunotherapy protocols with DC.
机译:多细胞肿瘤球体(MCTS)是一种完善的3-D体外模型系统,可反映肿瘤微区和无血管微转移部位的体内病理生理状况。因为单核细胞和其他免疫细胞会渗透到不同来源的MCTS中,所以这种球状共培养物是系统研究肿瘤与免疫细胞之间异源相互作用的有价值但仍被低估的工具。本文简要概述了已发表的关于MCTS中肿瘤与免疫细胞相互作用的研究成果,并总结了针对骨髓细胞的肿瘤环境中免疫抑制的机制。使用共培养模型,我们最近证明了肿瘤来源的乳酸是人类单核细胞的有效调节剂,因为乳酸抑制了单核细胞(MO)向树突状细胞(DC)的分化,也损害了抗原呈递。我们在本文中显示,MCTS中各种肿瘤细胞分泌乳酸的能力相差十倍,这表明该能力取决于肿瘤细胞类型。进一步证明乳酸可阻止MO向MCTS迁移,因为可以通过阻止乳酸的产生来增加渗透。因此,我们讨论了乳酸,它在许多肿瘤和肿瘤微区中积累,作为一种有效的免疫抑制剂,可有效抑制肿瘤环境中的MO / DC,并得出结论,这些数据与采用DC的过继免疫治疗方案高度相关。

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