Cross talk between cancer and immune cells: exploring complex dynamics in a microfluidic environment (original) (raw)

* Corresponding authors

a Italian National Research Council - Institute for Photonics and Nanotechnologies (CNR – IFN), Via Cineto Romano 42, Rome, Italy
E-mail: luca.businaro@cnr.it
Fax: +39 064152 2202
Tel: +39-064152 2265

b Istituto Superiore di Sanità, Dept of Hematology, Oncology and Molecular Medicine, Viale Regina Elena 299, Rome, Italy
E-mail: fabrizio.mattei@iss.it
Fax: +39-064990 2788
Tel: +39-0649902837

Abstract

The reconstitution of a complex microenvironment on microfluidic chips is one of the cornerstones to demonstrate the improved flexibility of these devices with respect to macroscale in vitro approaches. In this work, we realised an on-chip model to investigate the interactions between cancer and immune system. To this end, we exploited mice deficient (Knock Out, KO) for interferon regulatory factor 8 (IRF-8), a transcription factor essential for the induction of competent immune responses, to investigate how IRF-8 gene expression contributes to regulate immune and melanoma cells crosstalk. In vivo, IRF-8 KO mice are highly permissive to B16 melanoma growth due to failure of immune cells to properly exert immunosurveillance. B16 cells and immune cells isolated from the spleen of wild type (WT) and IRF-8 KO mice were co-cultured for one week in a PDMS platform and monitored by fluorescence microscopy and time-lapse recordings. We observed that WT spleen cells migrated through microchannels connecting the culturing chambers towards B16 cells and tightly interacted with tumor cells, forming clusters of activation. In contrast, IRF-8 KO immune cells poorly interacted with melanoma cells. In parallel, B16 cells were more attracted towards microchannels, acquiring a more invasive behaviour in the presence of IRF-8 KO spleen cells, with respect to WT cells. Our results strongly confirm the in vivo observations and highlight the value of on-chip co-culture systems as a useful in vitro tool to elucidate the reciprocal interactions between cancer cells and host immune system, with relevant impact in the development of more effective anti-tumor therapeutic strategies.

Graphical abstract: Cross talk between cancer and immune cells: exploring complex dynamics in a microfluidic environment

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Article information

DOI

https://doi.org/10.1039/C2LC40887B

Article type

Paper

Submitted

03 Aug 2012

Accepted

27 Sep 2012

First published

01 Oct 2012

Download Citation

Lab Chip, 2013,13, 229-239

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