A multidisciplinary study using in vivo tumor models and microfluidic cell-on-chip approach to explore the cross-talk between cancer and immune cells

Fabrizio Mattei, Giovanna Schiavoni, Adele De Ninno, Valeria Lucarini, Paola Sestili, Antonella Sistigu, Alessandra Fragale, Massimo Sanchez, Massimo Spada, Annamaria Gerardino, Filippo Belardelli, Luca Businaro, Lucia Gabriele

Research output: Contribution to journalArticle

Abstract

A full elucidation of events occurring inside the cancer microenvironment is fundamental for the optimization of more effective therapies. In the present study, the cross-talk between cancer and immune cells was examined by employing mice deficient (KO) in interferon regulatory factor (IRF)-8, a transcription factor essential for induction of competent immune responses. The in vivo results showed that IRF-8 KO mice were highly permissive to B16.F10 melanoma growth and metastasis due to failure of their immune cells to exert proper immunosurveillance. These events were found to be dependent on soluble factors released by cells of the immune system capable of shaping the malignant phenotype of melanoma cells. An on-chip model was then generated to further explore the reciprocal interactions between the B16.F10 and immune cells. B16.F10 and immune cells were co-cultured in a microfluidic device composed of three culturing chambers suitably inter-connected by an array of microchannels; mutual interactions were then followed using time-lapse microscopy. It was observed that WT immune cells migrated through the microchannels towards the B16.F10 cells, establishing tight interactions that in turn limited tumor spread. In contrast, IRF-8 KO immune cells poorly interacted with the melanoma cells, resulting in a more invasive behavior of the B16.F10 cells. These results suggest that IRF-8 expression plays a key role in the cross-talk between melanoma and immune cells, and under-score the value of cell-on-chip approaches as useful in vitro tools to reconstruct complex in vivo microenvironments on a microscale level to explore cell interactions such as those occurring within a cancer immunoenvironment.

Original languageEnglish
Pages (from-to)337-346
Number of pages10
JournalJournal of Immunotoxicology
Volume11
Issue number4
DOIs
Publication statusPublished - Oct 1 2014

Keywords

  • Immune cells
  • IRF-8
  • Melanoma
  • Microfluidics
  • Mouse tumor model
  • Tumor microenvironment

ASJC Scopus subject areas

  • Toxicology
  • Immunology
  • Medicine(all)

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  • Cite this

    Mattei, F., Schiavoni, G., De Ninno, A., Lucarini, V., Sestili, P., Sistigu, A., Fragale, A., Sanchez, M., Spada, M., Gerardino, A., Belardelli, F., Businaro, L., & Gabriele, L. (2014). A multidisciplinary study using in vivo tumor models and microfluidic cell-on-chip approach to explore the cross-talk between cancer and immune cells. Journal of Immunotoxicology, 11(4), 337-346. https://doi.org/10.3109/1547691X.2014.891677