Immunotherapy on Chip: “Under the Microscope” Drug-induced Modulation of the Immune Response
Poster Aug 01, 2017
A. De Ninno (a), F. Bertani (a), A. Gerardino (a), F. Mattei (b), V. Lucarini (b), G. Schiavoni (b), S. Parlato (b), L. Gabriele (b), R. Molfetta (f), E. Martinelli (c), A. Mencattini (c), D. Di Giuseppe (c), C. Di Natale (c), G. Kroemer (d), E. Vacchelli (d), A. Rainer (e), S. Giannitelli(e), and L. Businaro(a)
We present our approach to perform and analyze immune system–cancer cross talk on chip experiments. Flanking in-vivo and in-vitro experiments with on chip co-cultures of primary human PBMC, immune cell subpopulations or murine spleen cells with melanoma, breast and colorectal cancer cells allowed us to test the on-chip model and to extract meaningful kinetics and behavioral data in the microfluidic controlled environments. The experimental setup allowed us to describe the effects of drugs or genetic modifications on the cell population crosstalk, highlighting or confirming important mechanisms in boosting the immune response against cancer. Our vision is that modern microscopy and on chip immune system reconstitution represent the needed bridge to link biology to advanced mathematical methods developed in complex system physics and to numerical simulation, allowing the development of integrated “cybernetic” models able to explore fundamental biology, and to tackle critical issues of drug testing with impact on clinical trials.
Genome-wide association studies (GWAS) have identified more than 100 genetic loci associated with type 2 diabetes. The majority of these are located in the intergenic or intragenic regions suggesting that the implicated variants may alter chromatin conformation. This, in turn, is likely to influence the expression of nearby or more remotely located genes to alter beta cell function. At present, however, detailed molecular and functional analyses are still lacking for most of these variants. We recently analysed one of these loci and mapped five causal variants in an islet-specific enhancer cluster within the STARD10 gene locus. Here, we aimed to understand how these causal variants influence b-cell function by alteration of the chromatin structure of enhancer clusterREAD MORE