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

• Published in: Nature communications Vol. 11; no. 1; p. 2749
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 02-06-2020; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 13/1; 13/106; 13/107; 13/21; 13/31; 14/63; 14/69; 38; 38/39; 631/1647; 631/1647/767; 631/1647/767/70; 631/67/1813; 631/67/1813/1634; Cancer; CD14 antigen; Cell Communication; Cell culture; Cell interactions; Cell Plasticity - physiology; Cell Survival; Coculture Techniques; Complexity; Dendritic cells; Dendritic Cells - metabolism; Dendritic plasticity; Dermis; Fibroblasts; Fibroblasts - pathology; Humanities and Social Sciences; Humans; Immune system; Immunotherapy; Keratinocytes; Keratinocytes - pathology; Melanoma; Melanoma - immunology; Melanoma - metabolism; Melanoma - pathology; Melanoma, Cutaneous Malignant; multidisciplinary; Phenotypes; Physiology; Science; Science (multidisciplinary); Skin - pathology; Skin cancer; Skin Neoplasms - immunology; Skin Neoplasms - metabolism; Skin Neoplasms - pathology; Tumor microenvironment; Tumor Microenvironment - immunology; Tumor Microenvironment - physiology; Tumors
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-16583-0

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.
Conventional co-culture systems often lack physiological complexity of the tumor microenvironment. Here, the authors report an organotypic skin melanoma culture and use this model to investigate the tumor induced suppression on dendritic cells.