scholarly journals Wide-field dynamic monitoring of immune cell trafficking in murine models of glioblastoma

2017 ◽  
Author(s):  
Elliott D. SoRelle ◽  
Derek Yecies ◽  
Orly Liba ◽  
F. Chris Bennett ◽  
Claus Moritz Graef ◽  
...  
Keyword(s):  
Immune Cell ◽  
Treatment Strategies ◽  
Dynamic Monitoring ◽  
Wide Field ◽  
Cell Trafficking ◽  
Cancer Proliferation ◽  
Field Dynamic ◽  
Longitudinal Imaging ◽  
Leukocyte Populations

AbstractLeukocyte populations, especially tumor-associated macrophages (TAMs), are capable of mediating both anti- and pro-tumor processes and play significant roles in the tumor microenvironment. Moreover, TAMs have been shown to exert substantial influence on the efficacy of various cancer immunotherapy treatment strategies. Laboratory investigation into the behavior of TAMs has been limited by a lack of methods capable of resolving the in vivo distribution and dynamics of this cell population across wide fields of view. Recent studies have employed magnetic resonance imaging and intravital microscopy in conjunction with nanoparticle labeling methods to detect TAMs and observe their responses to therapeutic agents. Here we describe a novel method to enable high-resolution, wide-field, longitudinal imaging of leukocytes based on contrast-enhanced Speckle-Modulating Optical Coherence Tomography (SM-OCT), which substantially reduces imaging noise. We were able to specifically label TAMs and activated microglia in vivo with large gold nanorod contrast agents (LGNRs) in an orthotopic murine glioblastoma model. After labeling, we demonstrated near real-time tracking of leukocyte migration and distribution within the tumors. The intrinsic resolution, imaging depth, and sensitivity of this method may facilitate detailed studies of the fundamental behaviors of TAMs in vivo, including their intratumoral distribution heterogeneity and the roles they play in modulating cancer proliferation. In future studies, the method described herein may also provide the necessary means to characterize TAM responses to immunotherapeutic regimens in a range of solid tumors.

scholarly journals Cellular MR Imaging

2005 ◽  
Vol 4 (3) ◽  
pp. 153535002005051 ◽  
Author(s):  
Michel Modo ◽  
Mathias Hoehn ◽  
Jeff W.M. Bulte
Keyword(s):  
Mr Imaging ◽  
Contrast Agents ◽  
Immune Cell ◽  
Late Phase ◽  
Superparamagnetic Iron Oxide ◽  
Cell Trafficking ◽  
Macrophage Activity ◽  
Active Research

Cellular MR imaging is a young field that aims to visualize targeted cells in living organisms. In order to provide a different signal intensity of the targeted cell, they are either labeled with MR contrast agents in vivo or prelabeled in vitro. Either (ultrasmall) superparamagnetic iron oxide [(U)SPIO] particles or (polymeric) paramagnetic chelates can be used for this purpose. For in vivo cellular labeling, Gd3+- and Mn2+- chelates have mainly been used for targeted hepatobiliary imaging, and (U)SPIO-based cellular imaging has been focused on imaging of macrophage activity. Several of these magneto-pharmaceuticals have been FDA-approved or are in late-phase clinical trials. As for prelabeling of cells in vitro, a challenge has been to induce a sufficient uptake of contrast agents into nonphagocytic cells, without affecting normal cellular function. It appears that this issue has now largely been resolved, leading to an active research on monitoring the cellular biodistribution in vivo following transplantation or transfusion of these cells, including cell migration and trafficking. New applications of cellular MR imaging will be directed, for instance, towards our understanding of hematopoietic (immune) cell trafficking and of novel guided (stem) cell-based therapies aimed to be translated to the clinic in the future.

scholarly journals Migration ofAntigen-Specific T Cells Away from CXCR4-Binding Human ImmunodeficiencyVirus Type 1gp120

2004 ◽  
Vol 78 (10) ◽  
pp. 5184-5193 ◽  
Author(s):  
Diana M. Brainard ◽  
William G. Tharp ◽  
Elva Granado ◽  
Nicholas Miller ◽  
Alicja K. Trocha ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Cell ◽  
Active Movement ◽  
Target Cells ◽  
Cell Mediated Immunity ◽  
Cell Trafficking ◽  
Hiv 1

ABSTRACT Cell-mediated immunity depends in part on appropriate migration and localization of cytotoxic T lymphocytes (CTL), a process regulated by chemokines and adhesion molecules. Many viruses, including human immunodeficiency virus type 1 (HIV-1), encode chemotactically active proteins, suggesting that dysregulation of immune cell trafficking may be a strategy for immune evasion. HIV-1 gp120, a retroviral envelope protein, has been shown to act as a T-cell chemoattractant via binding to the chemokine receptor and HIV-1 coreceptor CXCR4. We have previously shown that T cells move away from the chemokine stromal cell-derived factor 1 (SDF-1) in a concentration-dependent and CXCR4 receptor-mediated manner. Here, we demonstrate that CXCR4-binding HIV-1 X4 gp120 causes the movement of T cells, including HIV-specific CTL, away from high concentrations of the viral protein. This migratory response is CD4 independent and inhibited by anti-CXCR4 antibodies and pertussis toxin. Additionally, the expression of X4 gp120 by target cells reduces CTL efficacy in an in vitro system designed to account for the effect of cell migration on the ability of CTL to kill their target cells. Recombinant X4 gp120 also significantly reduced antigen-specific T-cell infiltration at a site of antigen challenge in vivo. The repellant activity of HIV-1 gp120 on immune cells in vitro and in vivo was shown to be dependent on the V2 and V3 loops of HIV-1 gp120. These data suggest that the active movement of T cells away from CXCR4-binding HIV-1 gp120, which we previously termed fugetaxis, may provide a novel mechanism by which HIV-1 evades challenge by immune effector cells in vivo.

Bioluminescent Method for Assaying Multiple Semicarbazide-Sensitive Amine Oxidase (SSAO) Family Members in Both 96- and 384-Well Formats

2011 ◽  
Vol 16 (9) ◽  
pp. 1106-1111 ◽  
Author(s):  
Gregory W. Peet ◽  
Susan Lukas ◽  
Melissa Hill-Drzewi ◽  
Leslie Martin ◽  
Irina V. Rybina ◽  
...  
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Immune Cell ◽  
Amine Oxidase ◽  
Inflammatory Diseases ◽  
Live Cells ◽  
Primary Amines ◽  
Cell Trafficking ◽  
Vascular Adhesion

Vascular adhesion protein–1 (VAP-1), also known as semicarbazide-sensitive amine oxidase (SSAO) or copper-containing amine oxidase (AOC3, EC 1.4.3.6), catalyzes oxidative deamination of primary amines. One endogenous substrate has recently been described (Siglec 10), and although its mechanism of action in vivo is not completely understood, it is suggested to play a role in immune cell trafficking, making it a target of interest for autoimmune and inflammatory diseases. Much of the enzymology performed around this target has been conducted with absorbance, fluorescent, or radiometric formats that can have some limitations for high-throughput screening and subsequent compound profiling. The authors present the use of a bioluminescent assay, originally developed for monoamine oxidase enzymes, in a high-throughput format. It can be used for related SSAOs such as AOC1 given their substrate similarity with VAP-1. The authors also demonstrate that it is compatible with different sources of VAP-1, both purified recombinant and VAP-1 overexpressed on live cells.

scholarly journals CDKN2B-AS1 Promotes Malignancy as a Novel Prognosis-Related Molecular Marker in the Endometrial Cancer Immune Microenvironment

2021 ◽  
Vol 9 ◽  
Author(s):  
Di Yang ◽  
Jian Ma ◽  
Xiao-Xin Ma
Keyword(s):  
Endometrial Cancer ◽  
Immune Cell ◽  
Quantitative Polymerase Chain Reaction ◽  
Treatment Strategies ◽  
Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Immune Infiltration ◽  
Lncrna Expression ◽  
Ec Cells

The prognosis of patients with endometrial cancer (EC) is closely associated with immune cell infiltration. Although abnormal long non-coding RNA (lncRNA) expression is also linked to poor prognosis in patients with EC, the function and action mechanism of immune infiltration-related lncRNAs underlying the occurrence and development of EC remains unclear. In this study, we analyzed lncRNA expression using The Cancer Genome Atlas and clinical data and identified six lncRNAs as prognostic markers for EC, all of which are associated with the infiltration of immune cell subtypes, as illustrated by ImmLnc database and ssGSEA analysis. Real-time quantitative polymerase chain reaction showed that CDKN2B-AS1 was significantly overexpressed in EC, whereas its knockdown inhibited the proliferation and invasion of EC cells and the in vivo growth of transplanted tumors in nude mice. Finally, we constructed a competing endogenous RNA regulatory network and conducted Gene Ontology enrichment analysis to elucidate the potential molecular mechanism underlying CDKN2B-AS1 function. Overall, we identified molecular targets associated with immune infiltration and prognosis and provide new insights into the development of molecular therapies and treatment strategies against EC.

scholarly journals Monocyte Infection Dynamics Shape HIV-1 Phyloanatomy in the Peripheral Blood

2018 ◽  
Author(s):  
Brittany Rife Magalis ◽  
Samantha L. Strickland ◽  
Stephen D Shank ◽  
Patrick Autissier ◽  
Alexandra Schuetz ◽  
...  
Keyword(s):  
T Cell ◽  
Peripheral Blood ◽  
Immune Cell ◽  
Viral Evolution ◽  
Treatment Strategies ◽  
Immune Cell Population ◽  
Evolutionary Trajectory ◽  
Infection Dynamics ◽  
Monocyte Infection

Human immunodeficiency virus (HIV) RNA and DNA have been isolated from patient monocytes, an immune cell population that is quite different in several aspects from the canonical T-cell viral target. Because monocytes are migratory and resilient to both natural and synthetic antiviral defenses, knowledge of the contribution of monocyte infection to ongoing viral evolution and spread \textit{in vivo} is of significant interest for drug development and treatment strategies. Using single viral genome sequencing from different peripheral blood compartments and phyloanatomic statistical inference, we demonstrate that productively infected monocytes follow an evolutionary trajectory that is distinct from peripheral T cells during multiple stages of disease progression. Gene flow and selection analysis reveal plasticity in the source of monocyte infection and in the region of the HIV envelope glycoprotein that experiences selection pressure across individuals. The findings, thus, point to a potential reservoir showing a range of infection and transmission dynamics, for which the current universal, T cell-targeted treatment strategies would be inadequate.

scholarly journals OTEH-7. Molecular characterization of tumor stiffness in glioblastoma

2021 ◽  
Vol 3 (Supplement_2) ◽  
pp. ii11-ii12
Author(s):  
Skarphedinn Halldorsson ◽  
Siri Fløgstad Svensson ◽  
Henriette Engen Berg ◽  
Denise Wolrab ◽  
Frode Rise ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Immune Cell ◽  
Treatment Strategies ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Tissue Stiffness ◽  
Cancer Proliferation ◽  
Polar Metabolites ◽  
Novel Treatment Strategies ◽  
Tumor Stiffness

Abstract Tumor heterogeneity is one of the hallmarks of glioblastoma multiforme (GBM). Morphology within a given GBM tumor can be extremely variable where some regions of the tumor have a soft, gel-like structure while other areas are dense and fibrous. Abnormal mechanical stress and tissue stiffening caused by cancer proliferation are believed to affect vascularity by compressing structurally weak blood vessels and restricting the supply of nutrients and oxygen to the tissue. These effects contribute to a hypoxic microenvironment that promotes disease progression and chemoresistance. The genetic and molecular mechanisms that govern tissue stiffness within GBM tumors, however, are largely unknown. Magnetic Resonance Elastography (MRE) is an emerging technique for quantifying tissue stiffness non-invasively. We have evaluated 10 GBM patients by MRE imaging obtained prior to surgical resection. During surgery, 2–7 stereotactically navigated biopsies were collected from locations within the tumor with varying degrees of measured stiffness. Biopsies were processed to extract RNA, proteins, polar metabolites and lipids. Biomolecules were analyzed on relevant -omics platforms (RNA sequencing, MS-proteomics and lipidomics, NMR of polar metabolites). Differential expression and gene set enrichment analysis of patient paired biopsies indicate an overall increase in macrophage infiltration and extracellular matrix re-organization associated with increased tumor stiffness. Among the most highly upregulated genes in stiff tumor tissue were lymphatic endothelial hyaluronic acid receptor 1 (LYVE-1) and macrophage receptor with collagenous structure (MARCO), both of which have been associated with immune cell infiltration and tissue stiffness. Our preliminary findings offer novel insights into tumor morphology in GBM that can be inferred from imaging prior to surgery. This can be used to identify tumor regions with high risk of progression and infiltration, thereby informing and guiding surgical strategy and may ultimately lead to novel treatment strategies.

Understanding immune cell trafficking patterns via in vivo bioluminescence imaging

2002 ◽  
Vol 87 (S39) ◽  
pp. 239-248 ◽  
Author(s):  
Stefanie Mandl ◽  
Christoph Schimmelpfennig ◽  
Matthias Edinger ◽  
Robert S. Negrin ◽  
Christopher H. Contag
Keyword(s):  
Bioluminescence Imaging ◽  
Immune Cell ◽  
Cell Trafficking ◽  
Immune Cell Trafficking ◽  
In Vivo Bioluminescence Imaging

Engineering Tools for Studying the Interplay Between Mechanics and Biology in Lymphatic Lipid Transport

2010 ◽  
Author(s):  
J. Brandon Dixon
Keyword(s):  
Immune Cell ◽  
Mechanical Load ◽  
Contractile Function ◽  
Lymphatic Vessels ◽  
Dietary Lipid ◽  
The Body ◽  
Lipid Transport ◽  
Cell Trafficking

The lymphatic vasculature extends through most tissues of the body and plays an essential role in maintaining fluid balance, immune cell trafficking, and lipid transport. Nearly all dietary lipid is transported from the intestine to the circulation via the lymphatic system in the form of triglyceride-rich lipoproteins called chylomicrons. This process can be described through two different mechanisms: 1) entry of the chylomicron into the initial lymphatic vessels of the small intestine, known as lacteals, and 2) the transport of these chylomicrons through the larger collecting lymphatics by a complex and coordinated system of individual contracting vessel units (lymphangions) and valve leaflets. We describe here a set of in vitro and in vivo tools we have developed to study the mechanisms that modulate lipid transport under these two different paradigms and show how these tools are uncovering important biological features involved in these mechanisms. Lymphatic pump function is known to be sensitive to the mechanical load on the vessel as the contractility of isolated vessels has been shown to be both shear and stretch sensitive [1], yet whether these mechanisms are important in regulating contractile function in vivo remains uncertain.

In vivo imaging of immune cell trafficking in cancer

2010 ◽  
Vol 38 (5) ◽  
pp. 949-968 ◽  
Author(s):  
Luisa Ottobrini ◽  
Cristina Martelli ◽  
Daria Lucia Trabattoni ◽  
Mario Clerici ◽  
Giovanni Lucignani
Keyword(s):  
In Vivo Imaging ◽  
Immune Cell ◽  
Cell Trafficking ◽  
Immune Cell Trafficking

Histone methyltransferase SETDB1 promotes colorectal cancer proliferation through the STAT1-CCND1/CDK6 axis

2019 ◽  
Vol 41 (5) ◽  
pp. 678-688 ◽  
Author(s):  
Lu Yu ◽  
Feng Ye ◽  
Yi-Yi Li ◽  
Yi-Zhi Zhan ◽  
Yang Liu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Functional Characterization ◽  
Treatment Strategies ◽  
Histone Methyltransferase ◽  
Set Domain ◽  
Cancer Proliferation ◽  
Downstream Effector ◽  
Novel Treatment Strategies

Abstract Upregulation of histone methyltransferase SET domain bifurcated 1 (SETDB1) is associated with poor prognosis in cancer patients. However, the mechanism of oncogenicity of SETDB1 in cancer is hitherto unknown. Here, we show that SETDB1 is upregulated in human colorectal cancer (CRC) where its level correlates with poor clinical outcome. Ectopic SETDB1 promotes CRC cell proliferation, whereas SETDB1 attenuation inhibits this process. Flow cytometry reveals that SETDB1 promotes proliferation by driving the CRC cell cycle from G0/G1 phase to S phase. Mechanistically, SETDB1 binds directly to the STAT1 promoter region resulting in increased STAT1 expression. Functional characterization reveals that STAT1-CCND1/CDK6 axis is a downstream effector of SETDB1-mediated CRC cell proliferation. Furthermore, SETDB1 upregulation is sufficient to accelerate in vivo proliferation in xenograft animal model. Taken together, our results provide insight into the upregulation of SETDB1 within CRC and can lead to novel treatment strategies targeting this cell proliferation-promoting gene.

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