Patient-specific vascularized tumor model: Blocking monocyte recruitment with multispecific antibodies targeting CCR2 and CSF-1R.

Tumor-associated inflammation drives cancer progression and therapy resistance, often linked to the infiltration of monocyte-derived tumor-associated macrophages (TAMs), which are associated with poor prognosis in various cancers. To advance immunotherapies, testing on immunocompetent pre-clinical models of human tissue is crucial. We have developed an in vitro model of microvascular networks with tumor spheroids or patient tissues to assess monocyte trafficking into tumors and evaluate immunotherapies targeting the human tumor microenvironment.

Patient-Specific Vascularized Tumor Model: Blocking TAM Recruitment with Multispecific Antibodies Targeting CCR2 and CSF-1R.

Tumor-associated inflammation drives cancer progression and therapy resistance, with the infiltration of monocyte-derived tumor-associated macrophages (TAMs) associated with poor prognosis in diverse cancers. Targeting TAMs holds potential against solid tumors, but effective immunotherapies require testing on immunocompetent human models prior to clinical trials. Here, we develop an in vitro model of microvascular networks that incorporates tumor spheroids or patient tissues.

A Human Neurovascular Unit On-a-Chip.

Protection of the central nervous system (CNS) and cerebral homeostasis depend upon the blood-brain barrier (BBB) functions and permeability. BBB restrictive permeability hinders drug delivery for the treatment of several neurodegenerative diseases and brain tumors. Several in vivo animal models and in vitro systems have been developed to understand the BBB complex mechanisms and aid in the design of improved therapeutic strategies.

Tumor-Derived cGAMP Regulates Activation of the Vasculature.

Intratumoral recruitment of immune cells following innate immune activation is critical for anti-tumor immunity and involves cytosolic dsDNA sensing by the cGAS/STING pathway. We have previously shown that KRAS-LKB1 (KL) mutant lung cancer, which is resistant to PD-1 blockade, exhibits silencing of STING, impaired tumor cell production of immune chemoattractants, and T cell exclusion. Since the vasculature is also a critical gatekeeper of immune cell infiltration into tumors, we developed a novel microfluidic model to study KL tumor-vascular interactions.

Integrated in silico and 3D in vitro model of macrophage migration in response to physical and chemical factors in the tumor microenvironment.

Macrophages are abundant in the tumor microenvironment (TME), serving as accomplices to cancer cells for their invasion. Studies have explored the biochemical mechanisms that drive pro-tumor macrophage functions; however the role of TME interstitial flow (IF) is often disregarded. Therefore, we developed a three-dimensional microfluidic-based model with tumor cells and macrophages to study how IF affects macrophage migration and its potential contribution to cancer invasion.

Modeling Nanocarrier Transport across a 3D In Vitro Human Blood-Brain-Barrier Microvasculature.

Polymer nanoparticles (NPs), due to their small size and surface functionalization potential have demonstrated effective drug transport across the blood-brain-barrier (BBB). Currently, the lack of in vitro BBB models that closely recapitulate complex human brain microenvironments contributes to high failure rates of neuropharmaceutical clinical trials. In this work, a previously established microfluidic 3D in vitro human BBB model, formed by the self-assembly of human-induced pluripotent stem cell-derived endothelial cells, primary brain pericytes, and astrocytes in triculture within a 3D fibrin hydrogel is exploited to quantify polymer NP permeability, as a function of size and surface chemistry.

MicroRNA delivery through nanoparticles.

MicroRNAs (miRNAs) are attracting a growing interest in the scientific community due to their central role in the etiology of major diseases. On the other hand, nanoparticle carriers offer unprecedented opportunities for cell specific controlled delivery of miRNAs for therapeutic purposes. This review critically discusses the use of nanoparticles for the delivery of miRNA-based therapeutics in the treatment of cancer and neurodegenerative disorders and for tissue regeneration.

Quantitative screening of the effects of hyper-osmotic stress on cancer cells cultured in 2- or 3-dimensional settings.

The maintenance of precise cell volume is critical for cell survival. Changes in extracellular osmolarity affect cell volume and may impact various cellular processes such as mitosis, mitochondrial functions, DNA repair as well as cell migration and proliferation. Much of what we know about the mechanisms of cell osmoregulation comes from in vitro two-dimensional (2D) assays that are less physiologically relevant than three-dimensional (3D) in vitro or in vivo settings.

Targeting immune cells for cancer therapy.

Recent years have seen a renaissance in the research linking inflammation and cancer with immune cells playing a central role in smouldering inflammation in the tumor microenvironment. Diverse immune cell types infiltrate the tumor microenvironment, and the dynamic tumor-immune cell interplay gives rise to a rich milieu of cytokines and growth factors. Fundamentally, this intricate cross-talk creates the conducive condition for tumor cell proliferation, survival and metastasis.

Corrigendum: Characterizing the Role of Monocytes in T Cell Cancer Immunotherapy Using a 3D Microfluidic Model.

[This corrects the article DOI: 10.3389/fimmu.2018.

Characterizing the Role of Monocytes in T Cell Cancer Immunotherapy Using a 3D Microfluidic Model.

In the hepatitis B virus (HBV)-related hepatocellular carcinoma tumor microenvironment (TME), monocytes reportedly impede natural T cell functions PD-L1/PD-1 signaling. However, it remains unclear if T cell receptor-redirected T cells (TCR T cells) are similarly inhibited. Hence, we developed a 3D intrahepatic TME microfluidic model to investigate the immunosuppressive potential of monocytes toward HBV-specific TCR T cells and the role of PD-L1/PD-1 signaling.

Quantifying Vascular Distribution and Adhesion of Nanoparticles with Protein Corona in Microflow.

The protein corona has emerged as an important determinant of biological response in nanoparticle (NP) drug delivery. However, there is presently no reported study on how the protein corona affects the behavior of NPs in microflow and its subsequent interactions with the vascular endothelium, which could affect their delivery to the target tumor site regardless of its targeting mechanism. Furthermore, a consensus on the role of physical and surface characteristics of NPs in affecting the margination of NPs is lacking due to different methods of quantifying margination.