title: Cross talk between cancer and immune cells: exploring complex dynamics in a microfluidic environment.
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.
authors.affiliation: Italian National Research Council-Institute for Photonics and Nanotechnologies (CNR-IFN), Via Cineto Romano 42, Rome, 00156, Italy. luca.businaro@cnr.it
authors.forename: Luca
authors.initials: L
authors.lastname: Businaro
authors.forename: Adele
authors.initials: A
authors.lastname: De Ninno
authors.forename: Giovanna
authors.initials: G
authors.lastname: Schiavoni
authors.forename: Valeria
authors.initials: V
authors.lastname: Lucarini
authors.forename: Gabriele
authors.initials: G
authors.lastname: Ciasca
authors.forename: Annamaria
authors.initials: A
authors.lastname: Gerardino
authors.forename: Filippo
authors.initials: F
authors.lastname: Belardelli
authors.forename: Lucia
authors.initials: L
authors.lastname: Gabriele
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Mattei
mesh_terms: D000818:Animals; D002450:Cell Communication / Q000502:physiology*; D002465:Cell Movement; D002478:Cells, Cultured; D018920:Coculture Techniques; D005434:Flow Cytometry; D050835:Interferon Regulatory Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008545:Melanoma / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation / Q000379:methods*; D008856:Microscopy, Fluorescence; D013154:Spleen / Q000166:cytology*; D013312:Stress, Physiological; D059008:Time-Lapse Imaging; D000099185:Interferon Regulatory Factor-8
chemical_list: D050835:Interferon Regulatory Factors; D000099185:Interferon Regulatory Factor-8