"In vitro" 3D models of tumor-immune system interaction

Adv Drug Deliv Rev. 2014 Dec 15:79-80:145-54. doi: 10.1016/j.addr.2014.05.003. Epub 2014 May 9.


Interaction between cancer cells and immune system critically affects development, progression and treatment of human malignancies. Experimental animal models and conventional "in vitro" studies have provided a wealth of information on this interaction, currently used to develop immune-mediated therapies. Studies utilizing three-dimensional culture technologies have emphasized that tumor architecture dramatically influences cancer cell-immune system interaction by steering cytokine production and regulating differentiation patterns of myeloid cells, and decreasing the sensitivity of tumor cells to lymphocyte effector functions. Hypoxia and increased production of lactic acid by tumor cells cultured in 3D architectures appear to be mechanistically involved. 3D culture systems could be further developed to (i) include additional cell partners potentially influencing cancer cell-immune system interaction, (ii) enable improved control of hypoxia, and (iii) allow the use of freshly derived clinical cancer specimens. Such advanced models will represent new tools for cancer immunobiology studies and for pre-clinical assessment of innovative treatments.

Keywords: Cancer; Hypoxia; Immune system; Perfusion bioreactors; Three-dimensional cultures.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Culture Techniques
  • Cell Differentiation
  • Cell Hypoxia / immunology
  • Cytokines / immunology
  • Disease Progression
  • Humans
  • In Vitro Techniques
  • Lactic Acid / metabolism
  • Models, Biological*
  • Neoplasms / immunology*
  • Neoplasms / pathology
  • Neoplasms / therapy


  • Cytokines
  • Lactic Acid