Immunotherapy efficacy relies on the crosstalk within the tumor microenvironment between cancer and dendritic cells (DCs) resulting in the induction of a potent and effective antitumor response. DCs have the specific role of recognizing cancer cells, taking up tumor antigens (Ags) and then migrating to lymph nodes for Ag (cross)-presentation to naïve T cells. Interferon-α-conditioned DCs (IFN-DCs) exhibit marked phagocytic activity and the special ability of inducing Ag-specific T-cell response. Here, we have developed a novel microfluidic platform recreating tightly interconnected cancer and immune systems with specific 3D environmental properties, for tracking human DC behaviour toward tumor cells. By combining our microfluidic platform with advanced microscopy and a revised cell tracking analysis algorithm, it was possible to evaluate the guided efficient motion of IFN-DCs toward drug-treated cancer cells and the succeeding phagocytosis events. Overall, this platform allowed the dissection of IFN-DC-cancer cell interactions within 3D tumor spaces, with the discovery of major underlying factors such as CXCR4 involvement and underscored its potential as an innovative tool to assess the efficacy of immunotherapeutic approaches.

Highlights d A complex HER2 + breast cancer ecosystem is reconstituted and quantitatively described d The effects of the drug trastuzumab (Herceptin) are directly visualized ex vivo d Trastuzumab promotes long cancer-immune interactions and an ADCC immune response d Trastuzumab and CAFs have antagonist immunomodulation effects

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In this paper we discuss the applicability of numerical descriptors and statistical physics concepts to characterize complex biological systems observed at microscopic level through organ on chip approach. To this end, we employ data collected on a microfluidic platform in which leukocytes can move through suitably built channels toward their target. Leukocyte behavior is recorded by standard time lapse imaging. In particular, we analyze three groups of human peripheral blood mononuclear cells (PBMC): heterozygous mutants (in which only one copy of the FPR1 gene is normal), homozygous mutants (in which both alleles encoding FPR1 are loss-of-function variants) and cells from ‘wild type’ donors (with normal expression of FPR1). We characterize the migration of these cells providing a quantitative confirmation of the essential role of FPR1 in cancer chemotherapy response. Indeed wild type PBMC perform biased random walks toward chemotherapy-treated cancer cells establishing persistent interactions with them. Conversely, heterozygous mutants present a weaker bias in their motion and homozygous mutants perform rather uncorrelated random walks, both failing to engage with their targets. We next focus on wild type cells and study the interactions of leukocytes with cancerous cells developing a novel heuristic procedure, inspired by Lyapunov stability in dynamical systems.

We hypothesize that quantification of structural similarity or dissimilarity between paired mammographic regions can be effective in detecting asymmetric signs of breast cancer. Bilateral masking procedures are applied for this purpose by using automatically detected anatomical landmarks. Changes in structural information of the extracted regions are investigated using spherical semivariogram descriptors and correlation-based structural similarity indices in the spatial and complex wavelet domains. The spatial distribution of grayscale values as well as of the magnitude and phase responses of multidirectional Gabor filters are used to represent the structure of mammographic density and of the directional components of breast tissue patterns, respectively. A total of 188 mammograms from the DDSM and mini-MIAS databases, consisting of 47 asymmetric cases and 47 normal cases, were analyzed. For the combined dataset of mammograms, areas under the receiver operating characteristic curves of 0.83, 0.77, and 0.87 were obtained, respectively, with linear discriminant analysis, the Bayesian classifier, and an artificial neural network with radial basis functions, using the features selected by stepwise logistic regression and leave-one-patient-out cross-validation. Two-view analysis provided accuracy up to 0.94, with sensitivity and specificity of 1 and 0.88, respectively.