title: Cancer-driven dynamics of immune cells in a microfluidic environment.
abstract: Scope of the present work is to infer the migratory ability of leukocytes by stochastic processes in order to distinguish the spontaneous organization of immune cells against an insult (namely cancer). For this purpose, spleen cells from immunodeficient mice, selectively lacking the transcription factor IRF-8 (IRF-8 knockout; IRF-8 KO), or from immunocompetent animals (wild-type; WT), were allowed to interact, alternatively, with murine B16.F10 melanoma cells in an ad hoc microfluidic environment developed on a LabOnChip technology. In this setting, only WT spleen cells were able to establish physical interactions with melanoma cells. Conversely, IRF-8 KO immune cells exhibited poor dynamical reactivity towards the neoplastic cells. In the present study, we collected data on the motility of these two types of spleen cells and built a complete set of observables that recapitulate the biological complexity of the system in these experiments. With remarkable accuracy, we concluded that the IRF-8 KO cells performed pure uncorrelated random walks, while WT splenocytes were able to make singular drifted random walks that collapsed on a straight ballistic motion for the system as a whole, hence giving rise to a highly coordinate response. These results may provide a useful system to quantitatively analyse the real time cell-cell interactions and to foresee the behavior of immune cells with tumor cells at the tissue level.
authors.affiliation: Dipartimento di Fisica, Sapienza Università di Roma.
authors.forename: Elena
authors.initials: E
authors.lastname: Agliari
authors.affiliation: Dipartimento di Fisica, Sapienza Università di Roma.
authors.forename: Elena
authors.initials: E
authors.lastname: Biselli
authors.affiliation: UCBM-CNR Joint Lab for Nanotechnologies for the Life Sciences, Università Campus Bio-Medico di Roma, Rome, Italy.
authors.forename: Adele
authors.initials: A
authors.lastname: De Ninno
authors.affiliation: Istituto Superiore di Sanità, Dept. of Hematology Oncology and Molecular Medicine, Roma.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Schiavoni
authors.affiliation: Istituto Superiore di Sanità, Dept. of Hematology Oncology and Molecular Medicine, Roma.
authors.forename: Lucia
authors.initials: L
authors.lastname: Gabriele
authors.affiliation: Istituto di Fotonica e Nanotecnologie, Consiglio Nazionale delle Ricerche, Roma.
authors.forename: Anna
authors.initials: A
authors.lastname: Gerardino
authors.affiliation: Istituto Superiore di Sanità, Dept. of Hematology Oncology and Molecular Medicine, Roma.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Mattei
authors.affiliation: Dipartimento di Fisica, Sapienza Università di Roma.
authors.forename: Adriano
authors.initials: A
authors.lastname: Barra
authors.affiliation: Istituto di Fotonica e Nanotecnologie, Consiglio Nazionale delle Ricerche, Roma.
authors.forename: Luca
authors.initials: L
authors.lastname: Businaro
mesh_terms: D000818:Animals; D002465:Cell Movement; D018920:Coculture Techniques; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics*; D007962:Leukocytes / Q000378:metabolism / Q000473:pathology*; D008546:Melanoma, Experimental / Q000235:genetics / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D013154:Spleen / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D013160:Splenic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000099185:Interferon Regulatory Factor-8
chemical_list: D050835:Interferon Regulatory Factors; D000099185:Interferon Regulatory Factor-8