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Brave Little World: Spheroids as an in vitro Model to Study Tumor-Immune-Cell Interactions
Eva Gottfried, Leoni A. Kunz-Schughart, Reinhard Andreesen and Marina Kreutz
volume 5 | issue 7
1 april 2006Pages: 691 - 695
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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 co-cultures 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 co-culture 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.
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDF If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.