The tumour microenvironment shapes dendritic cell plasticity in a human organotypic melanoma culture

Di Blasio, S.; Tazzari, M.; van Wigcheren, G.; van Duffelen, A.; Stefanini, I.; Bloemendal, M.; Gorris, M.; Vasaturo, A.; Bakdash, G.; Hato, S. V.; Schalkwijk, J.; de Vries, I. J. M.; van den Bogaard, E. H.; Figdor, C. G.

doi:10.1101/561530

bioRxiv · 10.1101/561530

The tumour microenvironment shapes dendritic cell plasticity in a human organotypic melanoma culture

Di Blasio, S.·Tazzari, M.·van Wigcheren, G.·van Duffelen, A.·Stefanini, I.·Bloemendal, M.·Gorris, M.·Vasaturo, A.·Bakdash, G.·Hato, S. V.·Schalkwijk, J.·de Vries, I. J. M.·van den Bogaard, E. H.·Figdor, C. G.

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Abstract

The tumour microenvironment (TME) forms a major obstacle in effective cancer treatment and for clinical success of immunotherapy. Conventional co-cultures have shed light into multiple aspects of cancer immunobiology, but they are limited by the lack of physiological complexity. We developed a novel human, organotypic skin melanoma culture (OMC) that allows real-time study of host-malignant cell interactions within a multi-cellular tissue architecture. By co-culturing keratinocytes, fibroblasts and immune cells with melanoma cells, onto a de-cellularized dermis, we generated a reconstructed TME that closely recapitulates tumour growth as observed in human lesions and supports cell survival and function. We demonstrate that the OMC is suitable and outperforms conventional 2D co-cultures for the study of TME-imprinting mechanisms. Within the OMC we observed the tumour-driven conversion of cDC2s into CD14+ DCs, characterized by a an immunosuppressive phenotype. The OMC provides a valuable complement to current approaches to study the TME.

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Di Blasio, S., Tazzari, M., van Wigcheren, G., van Duffelen, A., Stefanini, I., Bloemendal, M., Gorris, M., Vasaturo, A., Bakdash, G., Hato, S. V., Schalkwijk, J., de Vries, I. J. M., van den Bogaard, E. H., Figdor, C. G.. 2019-02-27. The tumour microenvironment shapes dendritic cell plasticity in a human organotypic melanoma culture. https://doi.org/10.1101/561530

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