The tumour microenvironment shapes dendritic cell plasticity in a human organotypic melanoma culture
Stefania Di Blasio, Glenn F. van Wigcheren, Anouk M.D. Becker, Anne van Duffelen, Mark A.J. Gorris, Kiek Verrijp, Irene Stefanini, Gert‐Jan Bakker, Martine Bloemendal, Altuna Halilović, Angela Vasaturo, Ghaith Bakdash, Stanleyson V. Hato, Johannes H.W. de Wilt, Joost Schalkwijk, I. Jolanda M. de Vries, Johannes Textor, Ellen H. van den Bogaard, Marcella Tazzari, Carl G. Figdor
Abstract
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.