Antitumor immunity driven by intratumoral dendritic cells contributes to the efficacy of anthracycline-based chemotherapy in cancer. We identified a loss-of-function allele of the gene coding for formyl peptide receptor 1 (FPR1) that was associated with poor metastasis-free and overall survival in breast and colorectal cancer patients receiving adjuvant chemotherapy. The therapeutic effects of anthracyclines were abrogated in tumor-bearing Fpr1(-/-) mice due to impaired antitumor immunity. Fpr1-deficient dendritic cells failed to approach dying cancer cells and, as a result, could not elicit antitumor T cell immunity. Experiments performed in a microfluidic device confirmed that FPR1 and its ligand, annexin-1, promoted stable interactions between dying cancer cells and human or murine leukocytes. Altogether, these results highlight the importance of FPR1 in chemotherapy-induced anticancer immune responses.

We demonstrate that micrometre and sub-micrometre particles can be trapped, aggregated and concentrated in planar quadrupole electrode configurations by positive and negative dielectrophoresis. For particles less than in diameter, concentration is driven by thermal gradients, hydrodynamic effects and sedimentation forces. Liquid streaming is induced by the AC field itself via local heating and results, under special conditions, in vortices which improve the trapping efficiency. Microstructures were fabricated by electron-beam lithography and modified by UV laser ablation. They had typical gap dimensions between 500 nm and several micrometres. The theoretical and experimental results illustrate the basic principles of particle behaviour in ultra-miniaturized field traps filled with aqueous solutions. The smallest single particle that we could stably trap was a Latex bead of 650 nm. The smallest particles which were concentrated in the central part of the field trap were 14 nm in diameter. At high frequencies (in the megahertz range), field strengths up to 56 MV can be applied in the narrow gaps of 500 nm. Further perspectives for microparticle and macromolecular trapping are discussed.

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.

Zinoni, C.; Alloing, B.; Monat, C.; Zwiller, V.; Li, L.; Fiore, A.; Lunghi, L.; Gerardino, A.; Riedmatten, de, H.; Zbinden, H.; Gisin, N.