scholarly journals Imaging Immune Cells Using Fc Domain Probes in Mouse Cancer Xenograft Models

Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 300
Author(s):  
Wendy Bernhard ◽  
Kris Barreto ◽  
Ayman El-Sayed ◽  
John DeCoteau ◽  
C. Ronald Geyer
Keyword(s):  
Immune Response ◽  
Immune Cells ◽  
Near Infrared ◽  
Immune Cell ◽  
Cell Types ◽  
Blood Analysis ◽  
Fluorescent Imaging ◽  
Whole Body ◽  
Non Invasive ◽  
Xenograft Models

Tracking immune responses is complex due to the mixture of cell types, variability in cell populations, and the dynamic environment. Tissue biopsies and blood analysis can identify infiltrating and circulating immune cells; however, due to the dynamic nature of the immune response, these are prone to sampling errors. Non-invasive targeted molecular imaging provides a method to monitor immune response, which has advantages of providing whole-body images, being non-invasive, and allowing longitudinal monitoring. Three non-specific Fc-containing proteins were labeled with near-infrared dye IRDye800CW and used as imaging probes to assess tumor-infiltrating immune cells in FaDu and A-431 xenograft models. We showed that Fc domains localize to tumors and are visible by fluorescent imaging. This tumor localization appears to be based on binding tumor-associated immune cells and some xenografts showed higher fluorescent signals than others. The Fc domain alone bound to different human immune cell types. The Fc domain can be a valuable research tool to study innate immune response.

scholarly journals Identification of immune-based prostate cancer subtypes using mRNA expression

2020 ◽  
Author(s):  
Jukun Song ◽  
Song He ◽  
Wei Wang ◽  
Jiaming Su ◽  
Dongbo Yuan ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Immune Response ◽  
Immune Cells ◽  
Immune Cell ◽  
Molecular Classification ◽  
Cell Types ◽  
Functional Enrichment ◽  
Cell Infiltration ◽  
Cell Subpopulation ◽  
Immune Cell Infiltration

Abstract Background Immune infiltration of Prostate cancer (PCa) was highly related to clinical outcomes. However, previous works failed to elucidate the diversity of different immune cell types that make up the function of the immune response system. The aim of the study was to uncover the composition of TIICs in PCa utilizing the CIBERSORT algorithm and further reveal the molecular characteristics of PCa subtypes. Method In the present work, we employed the CIBERSORT method to evaluate the relative proportions of immune cell profiling in PCa and adjacent samples, normal samples. We analyzed the correlation between immune cell infiltration and clinical information. The tumor-infiltrating immune cells of the TCGA PCa cohort were analyzed for the first time. The fractions of 22 immune cell types were imputed to determine the correlation between each immune cell subpopulation and clinical feature. Three types of molecular classification were identified via R-package of “CancerSubtypes”. The functional enrichment was analyzed in each subtype. The submap and TIDE algorithm were used to predict the clinical response to immune checkpoint blockade, and GDSC was employed to screen chemotherapeutic targets for the potential treatment of PCa. Results In current work, we utilized the CIBERSORT algorithm to assess the relative proportions of immune cell profiling in PCa and adjacent samples, normal samples. We investigated the correlation between immune cell infiltration and clinical data. The tumor-infiltrating immune cells in the TCGA PCa cohort were analyzed. The 22 immune cells were also calculated to determine the correlation between each immune cell subpopulation and survival and response to chemotherapy. Three types of molecular classification were identified. Each subtype has specific molecular and clinical characteristics. Meanwhile, Cluster I is defined as advanced PCa, and is more likely to respond to immunotherapy. Conclusions Our results demonstrated that differences in immune response may be important drivers of PCa progression and response to treatment. The deconvolution algorithm of gene expression microarray data by CIBERSOFT provides useful information about the immune cell composition of PCa patients. In addition, we have found a subtype of immunopositive PCa subtype and will help to explore the reasons for the poor effect of PCa on immunotherapy, and it is expected that immunotherapy will be used to guide the individualized management and treatment of PCa patients.

scholarly journals 67 Immunometabolism – emerging concepts and potential applications in livestock

2019 ◽  
Vol 97 (Supplement_3) ◽  
pp. 101-101
Author(s):  
Barry J Bradford
Keyword(s):  
Immune System ◽  
Communication Networks ◽  
Immune Cells ◽  
Immune Cell ◽  
Cell Types ◽  
Whole Body ◽  
Phagocytic Cells ◽  
Adaptive Immune Cells ◽  
Potential Applications ◽  
Host Microbe Interactions

Abstract Our understanding of the immune system emerged from the study of disease processes and the communication networks used by various cell types to respond to pathogens. As with many aspects of physiology, this initial view was colored by the techniques available at the time. With technical advances beginning in the 1990, research in sepsis and obesity began to identify critical interactions between the immune system and metabolism. Our current understanding of these interactions is informed by two active but largely distinct research communities. Many in the field of immunology are utilizing cellular metabolism tools to understand mitochondrial function and fuel use in response to activation of innate and adaptive immune cells, especially as these relate to cancer. From another vantage point, many metabolic physiologists are now seeking to understand the importance of tissue-resident immune cells and immune signaling molecules in metabolic homeostasis and pathologies. Beyond human health implications of recent findings, a number of immunometabolism insights have informed our understanding of livestock health. In inflammatory events, phagocytic cells are activated, and the dramatic increase in oxidative metabolism is driven primarily by glucose use. Metabolism of healthy animals is also influenced by secretions from immune cells. Studies in mice indicate that appropriate host/microbe interactions (balancing protection and tolerance) are mediated by a network of immune cell types in the gut, which is critical to both absorptive and barrier functions of the gut. Adipose tissue immune cells regulate lipolytic rate, insulin sensitivity, and perhaps whole-body inflammatory tone. Local immune cell impacts on metabolism of other organs, including the liver and pancreas, are also emerging. Immunity and metabolism are tightly interwoven, and the evolving understanding of these links may enable nutritional or pharmacological strategies to enhance resilience to disease and alter nutrient partitioning in livestock.

scholarly journals Measuring host immune response status by simultaneous quantitative measurement of activity of signal transduction pathways that coordinate functional activity of immune cells from innate and adaptive immune system

2021 ◽  
Author(s):  
Wilbert Bouwman ◽  
Wim Verhaegh ◽  
Arie van Doorn ◽  
Anja van de Stolpe
Keyword(s):  
Immune Response ◽  
Immune Cells ◽  
Functional Activity ◽  
Immune Cell ◽  
Adaptive Immune Response ◽  
Cell Types ◽  
Activity Profile ◽  
Pathway Activity ◽  
Adaptive Immune

Abstract For many diseases, including cancer, viral infections such as COVID-19, bacterial infections, and auto-immune diseases, the immune response is a major determinant of progression, response to therapy, and clinical outcome. Innate and adaptive immune response are controlled by coordinated activity of multiple immune cell types. The functional activity state of immune cells is determined by cellular signal transduction pathways (STPs). A novel mRNA-based signaling pathway assay platform has been developed to quantitatively measure relevant STP activities in all types of immune cells and mixed immune cell samples for experimental and diagnostic purposes. We generated a STP activity profile, termed Immune-Pathway Activity Profile (I-PAP), for a variety of immune cell types in resting and activated state, and provide a first example for use in patient samples. Methods. The technology to measure STP activity has been described for androgen and estrogen receptor, PI3K, MAPK, TGFB;, Notch, NFkB, JAK-STAT1/2, and JAK-STAT3 pathways. STP activity was measured on Affymetrix expression microarray data from preclinical studies containing public data from different types of immune cells, resting/naive or immune-activated in vitro, to establish I-PAPs. Subsequently data from a clinical study on rheumatoid arthritis were analyzed. Results. I-PAPs of naive/resting and immune-activated CD4+ and CD8+ T cells, T helper cells, B cells, NK cells, monocytes, macrophages, and dendritic cells were established and in agreement with known experimental immunobiology. In whole blood samples of rheumatoid arthritis patients TGFβ pathway activity was increased; JAK-STAT3 pathway activity was selectively increased in female patients. In naive CD4+ Tregs TGFB; pathway activity was increased, while in memory T effector cells JAK-STAT3 pathway activity tended to increase, suggesting that these immune cell types contributed to whole blood analysis results. Conclusion. STP assay technology (currently being converted to qPCR-based assays) makes it possible to directly measure functional activity of cells of the innate and adaptive immune response enabling quantitative assessment of the immune response of an individual patient. Envisioned utility lies in (1) prediction and monitoring of response to immunomodulatory treatments for a variety of immune-mediated diseases, including RA; (2) uncovering novel treatment targets; (3) improvement and standardization of in vitro immunology research and drug development.

scholarly journals Whole Blood Transcriptome Analysis Reveals the Correlation between Specific Immune Cells and Septicemic Melioidosis

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Ke Xu ◽  
Dahua Xu ◽  
Hua Pei ◽  
Yunfan Quan ◽  
Jun Liu ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Cd8 T Cells ◽  
Immune Cells ◽  
Immune Cell ◽  
Expression Patterns ◽  
Multivariate Logistic Regression Analysis ◽  
Cell Types ◽  
Host Immune System ◽  
Resting Cells

Melioidosis is a serious infectious disease caused by the environmental Gram-negative bacillus Burkholderia pseudomallei. It has been shown that the host immune system, mainly comprising various types of immune cells, fights against the disease. The present study was to specify correlation between septicemic melioidosis and the levels of multiple immune cells. First, the genes with differential expression patterns between patients with septicemic melioidosis (B. pseudomallei) and health donors (control/healthy) were identified. These genes being related to cytokine binding, cell adhesion molecule binding, and MHC relevant proteins may influence immune response. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed 23 enriched immune response pathways. We further leveraged the microarray data to investigate the relationship between immune response and septicemic melioidosis, using the CIBERSORT analysis. Comparison of the percentages of 22 immune cell types in B. pseudomallei vs. control/healthy revealed that those of CD4 memory resting cells, CD8+ T cells, B memory cells, and CD4 memory activated cells were low, whereas those of M0 macrophages, neutrophils, and gamma delta T cells were high. The multivariate logistic regression analysis further revealed that CD8+ T cells, M0 macrophages, neutrophils, and naive CD4+ cells were strongly associated with the onset of septicemic melioidosis, and M2 macrophages and neutrophils were associated with the survival in septicemic melioidosis. Taken together, these data point to a complex role of immune cells on the development and progression of melioidosis.

scholarly journals Profiles of Peripheral Immune Cells of Uncomplicated COVID-19 Cases with Distinct Viral RNA Shedding Periods

Viruses ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 514
Author(s):  
Denise Utami Putri ◽  
Cheng-Hui Wang ◽  
Po-Chun Tseng ◽  
Wen-Sen Lee ◽  
Fu-Lun Chen ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Cells ◽  
Mononuclear Cells ◽  
Immune Cell ◽  
Severe Disease ◽  
Viral Rna ◽  
Disease Course ◽  
Peripheral Blood Mononuclear ◽  
Peripheral Immune Cells ◽  
Cell Profile

The heterogeneity of immune response to COVID-19 has been reported to correlate with disease severity and prognosis. While so, how the immune response progress along the period of viral RNA-shedding (VRS), which determines the infectiousness of disease, is yet to be elucidated. We aim to exhaustively evaluate the peripheral immune cells to expose the interplay of the immune system in uncomplicated COVID-19 cases with different VRS periods and dynamic changes of the immune cell profile in the prolonged cases. We prospectively recruited four uncomplicated COVID-19 patients and four healthy controls (HCs) and evaluated the immune cell profile throughout the disease course. Peripheral blood mononuclear cells (PBMCs) were collected and submitted to a multi-panel flowcytometric assay. CD19+-B cells were upregulated, while CD4, CD8, and NK cells were downregulated in prolonged VRS patients. Additionally, the pro-inflammatory-Th1 population showed downregulation, followed by improvement along the disease course, while the immunoregulatory cells showed upregulation with subsequent decline. COVID-19 patients with longer VRS expressed an immune profile comparable to those with severe disease, although they remained clinically stable. Further studies of immune signature in a larger cohort are warranted.

scholarly journals Quantitative Methodologies to Dissect Immune Cell Mechanobiology

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 851
Author(s):  
Veronika Pfannenstill ◽  
Aurélien Barbotin ◽  
Huw Colin-York ◽  
Marco Fritzsche
Keyword(s):  
Mechanical Properties ◽  
Immune Response ◽  
Time Scales ◽  
Immune Cells ◽  
Cell Mechanics ◽  
Immune Cell ◽  
Biological Significance ◽  
Force Generation ◽  
Tissue Microenvironment ◽  
And Behavior

Mechanobiology seeks to understand how cells integrate their biomechanics into their function and behavior. Unravelling the mechanisms underlying these mechanobiological processes is particularly important for immune cells in the context of the dynamic and complex tissue microenvironment. However, it remains largely unknown how cellular mechanical force generation and mechanical properties are regulated and integrated by immune cells, primarily due to a profound lack of technologies with sufficient sensitivity to quantify immune cell mechanics. In this review, we discuss the biological significance of mechanics for immune cells across length and time scales, and highlight several experimental methodologies for quantifying the mechanics of immune cells. Finally, we discuss the importance of quantifying the appropriate mechanical readout to accelerate insights into the mechanobiology of the immune response.

The Intersection of Metformin and Inflammation

2021 ◽  
Author(s):  
Leena P. Bharath ◽  
Barbara S. Nikolajczyk
Keyword(s):  
Mitochondrial Function ◽  
Immune Cells ◽  
Immune Cell ◽  
Cell Types ◽  
Remarkable Effect ◽  
Tumor Onset ◽  
Age Related ◽  
Immune Mediated ◽  
Autoimmune Conditions ◽  
Near Term

The biguanide metformin is the most commonly used antidiabetic drug. Recent studies show that metformin not only improves chronic inflammation by improving metabolic parameters but also has a direct anti-inflammatory effect. In light of these findings, it is essential to identify the inflammatory pathways targeted by metformin to develop a comprehensive understanding of the mechanisms of action of this drug. Commonly accepted mechanisms of metformin action include AMPK activation and inhibition of mTOR pathways, which are evaluated in multiple diseases. Additionally, metformin's action on mitochondrial function and cellular homeostasis processes such as autophagy, is of particular interest because of the importance of these mechanisms in maintaining cellular health. Both dysregulated mitochondria and failure of the autophagy pathways, the latter of which impair clearance of dysfunctional, damaged, or excess organelles, affect cellular health drastically and can trigger the onset of metabolic and age-related diseases. Immune cells are the fundamental cell types that govern the health of an organism. Thus, dysregulation of autophagy or mitochondrial function in immune cells has a remarkable effect on susceptibility to infections, response to vaccination, tumor onset, and the development of inflammatory and autoimmune conditions. Here we summarize the latest research on metformin's regulation of immune cell mitochondrial function and autophagy as evidence that new clinical trials on metformin with primary outcomes related to the immune system should be considered to treat immune-mediated diseases over the near term.

scholarly journals Toll-Like Receptor-Based Strategies for Cancer Immunotherapy

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Saghar Pahlavanneshan ◽  
Ali Sayadmanesh ◽  
Hamidreza Ebrahimiyan ◽  
Mohsen Basiri
Keyword(s):  
Cancer Immunotherapy ◽  
Immune Cells ◽  
Immune Cell ◽  
Cell Types ◽  
Genetically Engineered ◽  
Current Status ◽  
Tlr Signaling ◽  
Functional Roles ◽  
Immunotherapy Of Cancer ◽  
Signaling Components

Toll-like receptors (TLRs) are expressed and play multiple functional roles in a variety of immune cell types involved in tumor immunity. There are plenty of data on the pharmacological targeting of TLR signaling using agonist molecules that boost the antitumor immune response. A recent body of research has also demonstrated promising strategies for improving the cell-based immunotherapy methods by inducing TLR signaling. These strategies include systemic administration of TLR antagonist along with immune cell transfer and also genetic engineering of the immune cells using TLR signaling components to improve the function of genetically engineered immune cells such as chimeric antigen receptor-modified T cells. Here, we explore the current status of the cancer immunotherapy approaches based on manipulation of TLR signaling to provide a perspective of the underlying rationales and potential clinical applications. Altogether, reviewed publications suggest that TLRs make a potential target for the immunotherapy of cancer.

scholarly journals Neuroinflammation in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia and the Interest of Induced Pluripotent Stem Cells to Study Immune Cells Interactions With Neurons

2021 ◽  
Vol 14 ◽  
Author(s):  
Elise Liu ◽  
Léa Karpf ◽  
Delphine Bohl
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Immune System ◽  
Frontotemporal Dementia ◽  
Immune Cells ◽  
Immune Cell ◽  
Current Knowledge ◽  
Cell Types ◽  
Induced Pluripotent ◽  
Different Cell Types ◽  
Lateral Sclerosis

Inflammation is a shared hallmark between amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). For long, studies were conducted on tissues of post-mortem patients and neuroinflammation was thought to be only bystander result of the disease with the immune system reacting to dying neurons. In the last two decades, thanks to improving technologies, the identification of causal genes and the development of new tools and models, the involvement of inflammation has emerged as a potential driver of the diseases and evolved as a new area of intense research. In this review, we present the current knowledge about neuroinflammation in ALS, ALS-FTD, and FTD patients and animal models and we discuss reasons of failures linked to therapeutic trials with immunomodulator drugs. Then we present the induced pluripotent stem cell (iPSC) technology and its interest as a new tool to have a better immunopathological comprehension of both diseases in a human context. The iPSC technology giving the unique opportunity to study cells across differentiation and maturation times, brings the hope to shed light on the different mechanisms linking neurodegeneration and activation of the immune system. Protocols available to differentiate iPSC into different immune cell types are presented. Finally, we discuss the interest in studying monocultures of iPS-derived immune cells, co-cultures with neurons and 3D cultures with different cell types, as more integrated cellular approaches. The hope is that the future work with human iPS-derived cells helps not only to identify disease-specific defects in the different cell types but also to decipher the synergistic effects between neurons and immune cells. These new cellular tools could help to find new therapeutic approaches for all patients with ALS, ALS-FTD, and FTD.

scholarly journals Molecular mechanisms governing circulating immune cell heterogeneity across different species revealed by single cell sequencing

2021 ◽  
Author(s):  
Zhibin Li ◽  
chengcheng Sun ◽  
Fei Wang ◽  
Xiran Wang ◽  
Jiacheng Zhu ◽  
...  
Keyword(s):  
Single Cell ◽  
Immune Cells ◽  
Evolutionary Biology ◽  
Regulatory Networks ◽  
Molecular Mechanisms ◽  
Mononuclear Cells ◽  
Immune Cell ◽  
Cell Types ◽  
Genetic Regulatory Networks ◽  
Peripheral Blood Mononuclear

Background: Immune cells play important roles in mediating immune response and host defense against invading pathogens. However, insights into the molecular mechanisms governing circulating immune cell diversity among multiple species are limited. Methods: In this study, we compared the single-cell transcriptomes of 77 957 immune cells from 12 species using single-cell RNA-sequencing (scRNA-seq). Distinct molecular profiles were characterized for different immune cell types, including T cells, B cells, natural killer cells, monocytes, and dendritic cells. Results: The results revealed the heterogeneity and compositions of circulating immune cells among 12 different species. Additionally, we explored the conserved and divergent cellular cross-talks and genetic regulatory networks among vertebrate immune cells. Notably, the ligand and receptor pair VIM-CD44 was highly conserved among the immune cells. Conclusions: This study is the first to provide a comprehensive analysis of the cross-species single-cell atlas for peripheral blood mononuclear cells (PBMCs). This research should advance our understanding of the cellular taxonomy and fundamental functions of PBMCs, with important implications in evolutionary biology, developmental biology, and immune system disorders

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