scholarly journals Hypoxia and the phenomenon of immune exclusion

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Violena Pietrobon ◽  
Francesco M. Marincola
Keyword(s):  
Solid Tumors ◽  
Chromatin Remodeling ◽  
In Vivo Imaging ◽  
Ex Vivo ◽  
Cell Distribution ◽  
Common Phenomenon ◽  
Current State ◽  
Promising Strategy ◽  
Immune Exclusion

AbstractOver the last few years, cancer immunotherapy experienced tremendous developments and it is nowadays considered a promising strategy against many types of cancer. However, the exclusion of lymphocytes from the tumor nest is a common phenomenon that limits the efficiency of immunotherapy in solid tumors. Despite several mechanisms proposed during the years to explain the immune excluded phenotype, at present, there is no integrated understanding about the role played by different models of immune exclusion in human cancers. Hypoxia is a hallmark of most solid tumors and, being a multifaceted and complex condition, shapes in a unique way the tumor microenvironment, affecting gene transcription and chromatin remodeling. In this review, we speculate about an upstream role for hypoxia as a common biological determinant of immune exclusion in solid tumors. We also discuss the current state of ex vivo and in vivo imaging of hypoxic determinants in relation to T cell distribution that could mechanisms of immune exclusion and discover functional-morphological tumor features that could support clinical monitoring.

scholarly journals GFP-Aequorin Protein Sensor for Ex Vivo and In Vivo Imaging of Ca 2+ Dynamics in High-Ca 2+ Organelles

2016 ◽  
Vol 23 (6) ◽  
pp. 738-745 ◽  
Author(s):  
Paloma Navas-Navarro ◽  
Jonathan Rojo-Ruiz ◽  
Macarena Rodriguez-Prados ◽  
María Dolores Ganfornina ◽  
Loren L. Looger ◽  
...  
Keyword(s):  
In Vivo Imaging ◽  
Ex Vivo ◽  
Protein Sensor

scholarly journals Ex Vivo and In Vivo Imaging and Biodistribution of Aptamers Targeting the Human Matrix MetalloProtease-9 in Melanomas

PLoS ONE ◽  
2016 ◽  
Vol 11 (2) ◽  
pp. e0149387 ◽  
Author(s):  
David Kryza ◽  
Frédéric Debordeaux ◽  
Laurent Azéma ◽  
Aref Hassan ◽  
Olivier Paurelle ◽  
...  
Keyword(s):  
In Vivo Imaging ◽  
Ex Vivo ◽  
Matrix Metalloprotease

Ex vivo measurement of tissue distribution of a nitroxide radical after intravenous injection and its in vivo imaging using a rapid scan ESR-CT system

2000 ◽  
Vol 18 (2) ◽  
pp. 151-156 ◽  
Author(s):  
Hitoshi Togashi ◽  
Taku Matsuo ◽  
Haruhide Shinzawa ◽  
Yoshio Takeda ◽  
Li Shao ◽  
...  
Keyword(s):  
Tissue Distribution ◽  
Intravenous Injection ◽  
In Vivo Imaging ◽  
Ex Vivo ◽  
Nitroxide Radical ◽  
Rapid Scan ◽  
Ct System

scholarly journals In Vivo Imaging of Peripheral Benzodiazepine Receptors in Mouse Lungs: A Biomarker of Inflammation

2005 ◽  
Vol 4 (4) ◽  
pp. 7290.2005.05133 ◽  
Author(s):  
Matthew J. Hardwick ◽  
Ming-Kai Chen ◽  
Kwamena Baidoo ◽  
Martin G. Pomper ◽  
Tomás R. Guilarte
Keyword(s):  
In Vivo Imaging ◽  
Ex Vivo ◽  
Inflammatory Diseases ◽  
Imaging Techniques ◽  
Benzodiazepine Receptors ◽  
Small Animal ◽  
Small Animal Pet ◽  
Planar Imaging ◽  
Peripheral Benzodiazepine Receptors

The ability to visualize the immune response with radioligands targeted to immune cells will enhance our understanding of cellular responses in inflammatory diseases. Peripheral benzodiazepine receptors (PBR) are present in monocytes and neutrophils as well as in lung tissue. We used lipopolysaccharide (LPS) as a model of inflammation to assess whether the PBR could be used as a noninvasive marker of inflammation in the lungs. Planar imaging of mice administrated 10 or 30 mg/kg LPS showed increased [123I]-( R)-PK11195 radioactivity in the thorax 2 days after LPS treatment relative to control. Following imaging, lungs from control and LPS-treated mice were harvested for ex vivo gamma counting and showed significantly increased radioactivity above control levels. The specificity of the PBR response was determined using a blocking dose of nonradioactive PK11195 given 30 min prior to radiotracer injection. Static planar images of the thorax of nonradioactive PK11195 pretreated animals showed a significantly lower level of radiotracer accumulation in control and in LPS-treated animals ( p < .05). These data show that LPS induces specific increases in PBR ligand binding in the lungs. We also used in vivo small-animal PET studies to demonstrate increased [11C]-( R)-PK11195 accumulation in the lungs of LPS-treated mice. This study suggests that measuring PBR expression using in vivo imaging techniques may be a useful biomarker to image lung inflammation.

scholarly journals Convergent molecular, cellular, and cortical neuroimaging signatures of major depressive disorder

2020 ◽  
Vol 117 (40) ◽  
pp. 25138-25149
Author(s):  
Kevin M. Anderson ◽  
Meghan A. Collins ◽  
Ru Kong ◽  
Kacey Fang ◽  
Jingwei Li ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Negative Affect ◽  
Depressive Disorder ◽  
Single Cell ◽  
In Vivo Imaging ◽  
Ex Vivo ◽  
Integrated Analysis ◽  
Down Regulation ◽  
Major Depressive

Major depressive disorder emerges from the complex interactions of biological systems that span genes and molecules through cells, networks, and behavior. Establishing how neurobiological processes coalesce to contribute to depression requires a multiscale approach, encompassing measures of brain structure and function as well as genetic and cell-specific transcriptional data. Here, we examine anatomical (cortical thickness) and functional (functional variability, global brain connectivity) correlates of depression and negative affect across three population-imaging datasets: UK Biobank, Brain Genomics Superstruct Project, and Enhancing NeuroImaging through Meta Analysis (ENIGMA; combined n ≥ 23,723). Integrative analyses incorporate measures of cortical gene expression, postmortem patient transcriptional data, depression genome-wide association study (GWAS), and single-cell gene transcription. Neuroimaging correlates of depression and negative affect were consistent across three independent datasets. Linking ex vivo gene down-regulation with in vivo neuroimaging, we find that transcriptional correlates of depression imaging phenotypes track gene down-regulation in postmortem cortical samples of patients with depression. Integrated analysis of single-cell and Allen Human Brain Atlas expression data reveal somatostatin interneurons and astrocytes to be consistent cell associates of depression, through both in vivo imaging and ex vivo cortical gene dysregulation. Providing converging evidence for these observations, GWAS-derived polygenic risk for depression was enriched for genes expressed in interneurons, but not glia. Underscoring the translational potential of multiscale approaches, the transcriptional correlates of depression-linked brain function and structure were enriched for disorder-relevant molecular pathways. These findings bridge levels to connect specific genes, cell classes, and biological pathways to in vivo imaging correlates of depression.

scholarly journals Exosome: A New Player in Translational Nanomedicine

2020 ◽  
Vol 9 (8) ◽  
pp. 2380 ◽  
Author(s):  
Houssam Aheget ◽  
María Tristán-Manzano ◽  
Loubna Mazini ◽  
Marina Cortijo-Gutierrez ◽  
Pablo Galindo-Moreno ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Cell Types ◽  
Structural Features ◽  
Biologically Active ◽  
Biological Processes ◽  
New Approach ◽  
Current State ◽  
Exosome Biogenesis ◽  
Production Techniques

Summary: Exosomes are extracellular vesicles released by the vast majority of cell types both in vivo and ex vivo, upon the fusion of multivesicular bodies (MVBs) with the cellular plasma membrane. Two main functions have been attributed to exosomes: their capacity to transport proteins, lipids and nucleic acids between cells and organs, as well as their potential to act as natural intercellular communicators in normal biological processes and in pathologies. From a clinical perspective, the majority of applications use exosomes as biomarkers of disease. A new approach uses exosomes as biologically active carriers to provide a platform for the enhanced delivery of cargo in vivo. One of the major limitations in developing exosome-based therapies is the difficulty of producing sufficient amounts of safe and efficient exosomes. The identification of potential proteins involved in exosome biogenesis is expected to directly cause a deliberate increase in exosome production. In this review, we summarize the current state of knowledge regarding exosomes, with particular emphasis on their structural features, biosynthesis pathways, production techniques and potential clinical applications.

scholarly journals Synthesis, Ex Vivo Evaluation, and Radiolabeling of Potent 1,5-Diphenylpyrrolidin-2-one Cannabinoid Subtype-1 Receptor Ligands as Candidates for In Vivo Imaging

2008 ◽  
Vol 51 (18) ◽  
pp. 5833-5842 ◽  
Author(s):  
Sean R. Donohue ◽  
Joseph H. Krushinski ◽  
Victor W. Pike ◽  
Eyassu Chernet ◽  
Lee Phebus ◽  
...  
Keyword(s):  
In Vivo Imaging ◽  
Ex Vivo ◽  
Receptor Ligands

scholarly journals Supramolecular Encapsulation of Small-Ultra Red Fluorescent Proteins in Virus-Like Nanoparticles for Non-Invasive In Vivo Imaging Agents

2020 ◽  
Author(s):  
Fabian C. Herbert ◽  
Olivia Brohlin ◽  
Tyler Galbraith ◽  
Candace Benjamin ◽  
Cesar A. Reyes ◽  
...  
Keyword(s):  
In Vivo Imaging ◽  
Fluorescent Protein ◽  
Fluorescent Proteins ◽  
Ex Vivo ◽  
Imaging Agents ◽  
Non Invasive ◽  
Red Fluorescent Proteins ◽  
Ex Vivo Imaging

<div> <div> <div> <p>Icosahedral virus-like particles (VLPs) derived from bacteriophages Qβ and PP7 encapsulating small-ultra red fluorescent protein (smURFP) were produced using a versatile supramolecualr capsid dissassemble-reassemble approach. The generated fluorescent VLPs display identical structural properties to their non-fluorescent analogs. Encapsulated smURFP shows indistinguishable photochemical properties to its unencapsulated counterpart, exhibits outstanding stability towards pH, and produces bright in vitro images following phagocytosis by macrophages. In vivo imaging allows biodistribution to be imaged at different time points. Ex vivo imaging of intravenously administered encapsulated smURFP reveleas localization in the liver and </p> </div> </div> <div> <div> <p>kidneys after 2 h blood circulation and substantial elimination constructs as non-invasive in vivo imaging agents. </p> </div> </div> </div>

scholarly journals Tracking Adoptive T Cell Therapy Using Magnetic Particle Imaging

2020 ◽  
Author(s):  
Angelie Rivera-Rodriguez ◽  
Lan B. Hoang-Minh ◽  
Andreina Chiu-Lam ◽  
Nicole Sarna ◽  
Leyda Marrero-Morales ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Solid Tumors ◽  
Magnetic Particle ◽  
Ex Vivo ◽  
Intraventricular Administration ◽  
Magnetic Particle Imaging ◽  
Particle Imaging ◽  
The Brain

ABSTRACTAdoptive cellular therapy (ACT) is a potent strategy to boost the immune response against cancer. ACT is an effective treatment for blood cancers, such as leukemias and lymphomas, but faces challenges treating solid tumors and cancers in locations like the brain. A critical step for success of ACT immunotherapy is achieving efficient trafficking of T cells to solid tumors, and the non-invasive and quantitative tracking of adoptively transferred T cell biodistribution would accelerate its development. Here, we demonstrate the use of Magnetic Particle Imaging (MPI) to non-invasively track ACT T cells in vivo. Labeling T cells with the superparamagnetic iron oxide nanoparticle tracer ferucarbotran did not affect T cell viability, phenotype, or cytotoxic function in vitro. Following ACT, ferucarbotran-labeled T cells were detected and quantified using MPI ex vivo and in vivo, in a mouse model of invasive brain cancer. Proof-of-principle in vivo MPI demonstrated its capacity to detect labeled T cells in lungs and liver after intravenous administration and to monitor T cell localization in the brain after intraventricular administration. Ex vivo imaging using MPI and optical imaging suggests accumulation of systemically administered ferucarbotran-labeled T cells in the brain, where MPI signal from ferucarbotran tracers and fluorescently tagged T cells were observed. Ex vivo imaging also suggest differential accumulation of nanoparticles and viable T cells in other organs like the spleen and liver. These results support the use of MPI to track adoptively transferred T cells and accelerate the development of ACT treatments for brain tumors and other cancers.

Progress in Translational Regulatory T Cell Therapies for Type 1 Diabetes and Islet Transplantation

2020 ◽  
Author(s):  
Braulio A Marfil-Garza ◽  
Joshua Hefler ◽  
Mario Bermudez De Leon ◽  
Rena Pawlick ◽  
Nidheesh Dadheech ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Islet Transplantation ◽  
Ex Vivo ◽  
Severe Hypoglycemia ◽  
Cell Therapies ◽  
Current State ◽  
Cellular Transplantation ◽  
And Function

Abstract Regulatory T cells (Tregs) have become highly relevant in the pathophysiology and treatment of autoimmune diseases, such as type 1 diabetes (T1D). As these cells are known to be defective in T1D, recent efforts have explored ex vivo and in vivo Treg expansion and enhancement as a means for restoring self-tolerance in this disease. Given their capacity to also modulate alloimmune responses, studies using Treg-based therapies have recently been undertaken in transplantation. Islet transplantation provides a unique opportunity to study the critical immunological crossroads between auto- and alloimmunity. This procedure has advanced greatly in recent years, and reports of complete abrogation of severe hypoglycemia and long-term insulin independence have become increasingly reported. It is clear that cellular transplantation has the potential to be a true cure in T1D, provided the remaining barriers of cell supply and abrogated need for immune suppression can be overcome. However, the role that Tregs play in islet transplantation remains to be defined. Herein, we synthesize the progress and current state of Treg-based therapies in T1D and islet transplantation. We provide an extensive, but concise, background to understand the physiology and function of these cells and discuss the clinical evidence supporting potency and potential Treg-based therapies in the context of T1D and islet transplantation. Finally, we discuss some areas of opportunity and potential research avenues to guide effective future clinical application. This review provides a basic framework of knowledge for clinicians and researchers involved in the care of patients with T1D and islet transplantation.

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