The tumour microenvironment (TME) forms a major obstacle in effective cancer treatment and for clinical success of immunotherapy. Conventional co-cultures have shed light onto multiple aspects of cancer immunobiology, but they are limited by the lack of physiological complexity. We develop a human organotypic skin melanoma culture (OMC) that allows real-time study of host-malignant cell interactions within a multicellular tissue architecture. By co-culturing decellularized dermis with keratinocytes, fibroblasts and immune cells in the presence of melanoma cells, we generate a reconstructed TME that closely resembles 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 observe the tumour-driven conversion of cDC2s into CD14+ DCs, characterized by an immunosuppressive phenotype. The OMC provides a valuable approach to study how a TME affects the immune system.

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

Stefanini I.;
2020

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 onto multiple aspects of cancer immunobiology, but they are limited by the lack of physiological complexity. We develop a human organotypic skin melanoma culture (OMC) that allows real-time study of host-malignant cell interactions within a multicellular tissue architecture. By co-culturing decellularized dermis with keratinocytes, fibroblasts and immune cells in the presence of melanoma cells, we generate a reconstructed TME that closely resembles 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 observe the tumour-driven conversion of cDC2s into CD14+ DCs, characterized by an immunosuppressive phenotype. The OMC provides a valuable approach to study how a TME affects the immune system.
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https://www.nature.com/articles/s41467-020-16583-0.pdf
Di Blasio S.; van Wigcheren G.F.; Becker A.; van Duffelen A.; Gorris M.; Verrijp K.; Stefanini I.; Bakker G.J.; Bloemendal M.; Halilovic A.; Vasaturo A.; Bakdash G.; Hato S.V.; de Wilt J.H.W.; Schalkwijk J.; de Vries I.J.M.; Textor J.C.; van den Bogaard E.H.; Tazzari M.; Figdor C.G.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/1742304
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