scholarly journals Predator-Prey in Tumor-Immune Interactions: A Wrong Model or Just an Incomplete One?

2021 ◽  
Vol 12 ◽  
Author(s):  
Irina Kareva ◽  
Kimberly A. Luddy ◽  
Cliona O’Farrelly ◽  
Robert A. Gatenby ◽  
Joel S. Brown
Keyword(s):  
Immune System ◽  
Immune Cell ◽  
Interference Competition ◽  
Prey Type ◽  
Cell Types ◽  
Cell Populations ◽  
Natural Food ◽  
Predator Population ◽  
Predator Prey ◽  
Predator Prey Models

Tumor-immune interactions are often framed as predator-prey. This imperfect analogy describes how immune cells (the predators) hunt and kill immunogenic tumor cells (the prey). It allows for evaluation of tumor cell populations that change over time during immunoediting and it also considers how the immune system changes in response to these alterations. However, two aspects of predator-prey type models are not typically observed in immuno-oncology. The first concerns the conversion of prey killed into predator biomass. In standard predator-prey models, the predator relies on the prey for nutrients, while in the tumor microenvironment the predator and prey compete for resources (e.g. glucose). The second concerns oscillatory dynamics. Standard predator-prey models can show a perpetual cycling in both prey and predator population sizes, while in oncology we see increases in tumor volume and decreases in infiltrating immune cell populations. Here we discuss the applicability of predator-prey models in the context of cancer immunology and evaluate possible causes for discrepancies. Key processes include “safety in numbers”, resource availability, time delays, interference competition, and immunoediting. Finally, we propose a way forward to reconcile differences between model predictions and empirical observations. The immune system is not just predator-prey. Like natural food webs, the immune-tumor community of cell types forms an immune-web of different and identifiable interactions.

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 Enabling out-of-clinic human immunity studies via single-cell profiling of capillary blood

2020 ◽  
Author(s):  
Tatyana Dobreva ◽  
David Brown ◽  
Jong Hwee Park ◽  
Matt Thomson
Keyword(s):  
Gene Expression ◽  
Immune System ◽  
Environmental Factors ◽  
Single Cell ◽  
Immune Cell ◽  
Cell Types ◽  
Capillary Blood ◽  
Specific Gene ◽  
Human Immune ◽  
Over Time

AbstractAn individual’s immune system is driven by both genetic and environmental factors that vary over time. To better understand the temporal and inter-individual variability of gene expression within distinct immune cell types, we developed a platform that leverages multiplexed single-cell sequencing and out-of-clinic capillary blood extraction to enable simplified, cost-effective profiling of the human immune system across people and time at single-cell resolution. Using the platform, we detect widespread differences in cell type-specific gene expression between subjects that are stable over multiple days.SummaryIncreasing evidence implicates the immune system in an overwhelming number of diseases, and distinct cell types play specific roles in their pathogenesis.1,2 Studies of peripheral blood have uncovered a wealth of associations between gene expression, environmental factors, disease risk, and therapeutic efficacy.4 For example, in rheumatoid arthritis, multiple mechanistic paths have been found that lead to disease, and gene expression of specific immune cell types can be used as a predictor of therapeutic non-response.12 Furthermore, vaccines, drugs, and chemotherapy have been shown to yield different efficacy based on time of administration, and such findings have been linked to the time-dependence of gene expression in downstream pathways.21,22,23 However, human immune studies of gene expression between individuals and across time remain limited to a few cell types or time points per subject, constraining our understanding of how networks of heterogeneous cells making up each individual’s immune system respond to adverse events and change over time.

scholarly journals High-dimensional immune-profiling in cancer: implications for immunotherapy

2020 ◽  
Vol 8 (1) ◽  
pp. e000363 ◽  
Author(s):  
Samuel Chuah ◽  
Valerie Chew
Keyword(s):  
Immune System ◽  
Immune Cell ◽  
Positive Impact ◽  
Cell Types ◽  
High Dimensional ◽  
Host Immune System ◽  
Cancer Therapies ◽  
Quality Of Data ◽  
New Information ◽  
Immune Profiling

Immunotherapy is a rapidly growing field for cancer treatment. In contrast to conventional cancer therapies, immunotherapeutic strategies focus on reactivating the immune system to mount an antitumor response. Despite the encouraging outcome in clinical trials, a large proportion of patients still do not respond to treatment and many experience different degrees of immune-related adverse events. Furthermore, it is now increasingly appreciated that even many conventional cancer therapies such as radiotherapy could have a positive impact on the host immune system for better clinical response. Hence, there is a need to better understand tumor immunity in order to design immunotherapeutic strategies, especially evidence-based combination therapies, for improved clinical outcomes. With this aim, cancer research turned its attention to profiling the immune contexture of either the tumor microenvironment (TME) or peripheral blood to uncover mechanisms and biomarkers which might aid in precision immunotherapeutics. Conventional technologies used for this purpose were limited by the depth and dimensionality of the data. Advances in newer techniques have, however, greatly improved the breadth and depth, as well as the quantity and quality of data that can be obtained. The result of these advances is a wealth of new information and insights on how the TME could be affected by various immune cell-types, and how this might in turn impact the clinical outcome of cancer patients . We highlight herein some of the high-dimensional technologies currently employed in immune profiling in cancer and summarize the insights and potential benefits they could bring in designing better cancer immunotherapies.

scholarly journals Intracerebral Hemorrhage Leads to Infiltration of Several Leukocyte Populations with Concomitant Pathophysiological Changes

2008 ◽  
Vol 29 (1) ◽  
pp. 137-143 ◽  
Author(s):  
Matthew C Loftspring ◽  
Jeremiah McDole ◽  
Aigang Lu ◽  
Joseph F Clark ◽  
Aaron J Johnson
Keyword(s):  
Flow Cytometry ◽  
Immune System ◽  
Intracerebral Hemorrhage ◽  
Immune Cell ◽  
Adaptive Immune System ◽  
Fold Increase ◽  
Cytokine Signaling ◽  
Cell Populations ◽  
Stroke Subtype ◽  
Mortality And Morbidity

Intracerebral hemorrhage (ICH) is a stroke subtype with high rates of mortality and morbidity. The immune system, particularly complement and cytokine signaling, has been implicated in brain injury after ICH. However, the cellular immunology associated with ICH has been understudied. In this report, we use flow cytometry to quantitatively profile immune cell populations that infiltrate the brain 1 and 4 days post-ICH. At 1 day CD45hi GR-1+ cells were increased 2.0-fold compared with saline controls ( P ≤ 0.05); however, we did not observe changes in any other cell populations analyzed. At 4 days ICH mice presented with a 2.4-fold increase in CD45hi cells, a 1.9-fold increase in CD45hi GR-1 cells, a 3.4-fold increase in CD45hi GR-1+ cells, and most notably, a 1.7-fold increase in CD4+ cells ( P ≤ 0.05 for all groups), compared with control mice. We did not observe changes in the numbers of CD8+ cells or CD45lo cells ( P = 0.43 and 0.49, respectively). Thus, we have shown the first use of flow cytometry to analyze leukocyte infiltration in response to ICH. Our finding of a CD4 T-cell infiltrate is novel and suggests a role for the adaptive immune system in the response to ICH.

scholarly journals Full-Length Transcriptome: A Reliable Alternative for Single-Cell RNA-Seq Analysis in the Spleen of Teleost Without Reference Genome

2021 ◽  
Vol 12 ◽  
Author(s):  
Lixing Huang ◽  
Ying Qiao ◽  
Wei Xu ◽  
Linfeng Gong ◽  
Rongchao He ◽  
...  
Keyword(s):  
Data Analysis ◽  
B Cells ◽  
Single Cell ◽  
Reference Genome ◽  
Immune Cell ◽  
Cell Types ◽  
Full Length ◽  
Cell Populations ◽  
Epinephelus Coioides ◽  
Rna Seq

Fish is considered as a supreme model for clarifying the evolution and regulatory mechanism of vertebrate immunity. However, the knowledge of distinct immune cell populations in fish is still limited, and further development of techniques advancing the identification of fish immune cell populations and their functions are required. Single cell RNA-seq (scRNA-seq) has provided a new approach for effective in-depth identification and characterization of cell subpopulations. Current approaches for scRNA-seq data analysis usually rely on comparison with a reference genome and hence are not suited for samples without any reference genome, which is currently very common in fish research. Here, we present an alternative, i.e. scRNA-seq data analysis with a full-length transcriptome as a reference, and evaluate this approach on samples from Epinephelus coioides-a teleost without any published genome. We show that it reconstructs well most of the present transcripts in the scRNA-seq data achieving a sensitivity equivalent to approaches relying on genome alignments of related species. Based on cell heterogeneity and known markers, we characterized four cell types: T cells, B cells, monocytes/macrophages (Mo/MΦ) and NCC (non-specific cytotoxic cells). Further analysis indicated the presence of two subsets of Mo/MΦ including M1 and M2 type, as well as four subsets in B cells, i.e. mature B cells, immature B cells, pre B cells and early-pre B cells. Our research will provide new clues for understanding biological characteristics, development and function of immune cell populations of teleost. Furthermore, our approach provides a reliable alternative for scRNA-seq data analysis in teleost for which no reference genome is currently available.

scholarly journals The Immune System of Mesothelioma Patients: A Window of Opportunity for Novel Immunotherapies

2021 ◽  
Author(s):  
Fabio Nicolini ◽  
Massimiliano Mazza
Keyword(s):  
Immune System ◽  
Immune Cells ◽  
Immune Cell ◽  
Current Knowledge ◽  
Cell Types ◽  
Screening Strategies ◽  
Tertiary Lymphoid Structures ◽  
Lymphoid Structures ◽  
Review Current

The interplay between the immune system and the pleural mesothelium is crucial both for the development of malignant pleural mesothelioma (MPM) and for the response of MPM patients to therapy. MPM is heavily infiltrated by several immune cell types which affect the progression of the disease. The presence of organized tertiary lymphoid structures (TLSs) witness the attempt to fight the disease in situ by adaptive immunity which is often suppressed by tumor expressed factors. In rare patients physiological, pharmacological or vaccine-induced immune response is efficient, rendering their plasma a valuable resource of anti-tumor immune cells and molecules. Of particular interest are human antibodies targeting antigens at the tumor cell surface. Here we review current knowledge regarding MPM immune infiltration, MPM immunotherapy and the harnessing of this response to identify novel biologics as biomarkers and therapeutics through innovative screening strategies.

scholarly journals TrackSOM: mapping immune response dynamics through sequential clustering of time- and disease-course single-cell cytometry data

2021 ◽  
Author(s):  
Givanna Haryono Putri ◽  
Jonathan Chung ◽  
Davis N Edwards ◽  
Felix Marsh-Wakefield ◽  
Suat Dervish ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune System ◽  
West Nile Virus ◽  
Immune Cells ◽  
Immune Cell ◽  
West Nile Virus Infection ◽  
Cell Populations ◽  
Disease Course ◽  
Response Dynamics ◽  
Over Time

Mapping the dynamics of immune cell populations over time or disease-course is key to understanding immunopathogenesis and devising putative interventions. We present TrackSOM, an algorithm which delineates cellular populations and tracks their development over a time- or disease-course of cytometry datasets. We demonstrate TrackSOM-enabled elucidation of the immune response to West Nile Virus infection in mice, uncovering heterogeneous sub-populations of immune cells and relating their functional evolution to disease severity. TrackSOM is easy to use, encompasses few parameters, is quick to execute, and enables an integrative and dynamic overview of the immune system kinetics that underlie disease progression and/or resolution.

scholarly journals Single-cell RNA sequencing reveals micro-evolution of the stickleback immune system

2021 ◽  
Author(s):  
Lauren E Fuess ◽  
Daniel I Bolnick
Keyword(s):  
Immune System ◽  
Single Cell ◽  
Immune Cells ◽  
Gasterosteus Aculeatus ◽  
Immune Cell ◽  
Expression Profiles ◽  
Cell Types ◽  
Model Systems ◽  
System Structure ◽  
Ecological Processes

Pathogenic infection is an important driver of many ecological processes. Furthermore, variability in immune function is an important driver of differential infection outcomes. New evidence would suggest that immune variation extends to broad cellular structure of immune systems. However, variability at such broad levels is traditionally difficult to detect in non-model systems. Here we leverage single cell transcriptomic approaches to document signatures of microevolution of immune system structure in a natural system, the three-spined stickleback (Gasterosteus aculeatus). We sampled nine adult fish from three populations with variability in resistance to a cestode parasite, Schistocephalus solidus, to create the first comprehensive immune cell atlas for G. aculeatus. Eight major immune cell types, corresponding to major vertebrate immune cells, were identified. We were also able to document significant variation in both abundance and expression profiles of the individual immune cell types, among the three populations of fish. This variability may contribute to observed variability in parasite susceptibility. Finally, we demonstrate that identified cell type markers can be used to reinterpret traditional transcriptomic data. Combined our study demonstrates the power of single cell sequencing to not only document evolutionary phenomena (i.e. microevolution of immune cells), but also increase the power of traditional transcriptomic datasets.

scholarly journals Comprehensive multi-omics single-cell data integration reveals greater heterogeneity in the human immune system

2021 ◽  
Author(s):  
Congmin Xu ◽  
Junkai Yang ◽  
Astrid Kosters ◽  
Benjamin R Babcock ◽  
Peng Qiu ◽  
...  
Keyword(s):  
Immune System ◽  
Single Cell ◽  
Immune Cell ◽  
Cell Types ◽  
Cell Receptor ◽  
Surface Proteins ◽  
Cell Type ◽  
Human Immune System ◽  
Receptor Repertoire ◽  
Human Immune

Single-cell transcriptomics enables the definition of diverse human immune cell types across multiple tissue and disease contexts. Still, deeper biological understanding requires comprehensive integration of multiple single-cell omics (transcriptomic, proteomic, and cell receptor repertoire). To improve the identification of diverse cell types and the accuracy of cell-type classification in our multi-omics single-cell datasets, we developed SuPERR-seq, a novel analysis workflow to increase the resolution and accuracy of clustering and allow for the discovery and characterization of previously hidden cell subsets. We show that by incorporating information from cell-surface proteins and immunoglobulin transcript counts, we accurately remove cell doublets and prevent widespread cell-type misclassification. This approach uniquely improves the identification of heterogeneous cell types in the human immune system, including a novel subset of antibody-secreting cells in the bone marrow.

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.

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