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

Nat Commun. 2020 Jun 2;11(1):2749. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Communication
  • Cell Plasticity / physiology*
  • Cell Survival
  • Coculture Techniques
  • Dendritic Cells / metabolism*
  • Fibroblasts / pathology
  • Humans
  • Keratinocytes / pathology
  • Melanoma / immunology
  • Melanoma / metabolism*
  • Melanoma / pathology
  • Melanoma, Cutaneous Malignant
  • Skin / pathology
  • Skin Neoplasms / immunology
  • Skin Neoplasms / metabolism
  • Skin Neoplasms / pathology
  • Tumor Microenvironment / immunology
  • Tumor Microenvironment / physiology*