scholarly journals Immune Regulatory Processes of the Tumor Microenvironment under Malignant Conditions

2021 ◽  
Vol 22 (24) ◽  
pp. 13311
Author(s):  
Katrin Pansy ◽  
Barbara Uhl ◽  
Jelena Krstic ◽  
Marta Szmyra ◽  
Karoline Fechter ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Immune Responses ◽  
Cell Activation ◽  
Immune Cell ◽  
Immune Escape ◽  
Large Fraction ◽  
Immune Cell Activation ◽  
Regulatory Processes ◽  
Membrane Bound ◽  
Tumor Entities

The tumor microenvironment (TME) is a critical regulator of tumor growth, progression, and metastasis. Since immune cells represent a large fraction of the TME, they play a key role in mediating pro- and anti-tumor immune responses. Immune escape, which suppresses anti-tumor immunity, enables tumor cells to maintain their proliferation and growth. Numerous mechanisms, which have been intensively studied in recent years, are involved in this process, and based on these findings, novel immunotherapies have been successfully developed. Here, we review the composition of the TME and the mechanisms by which immune evasive processes are regulated. In detail, we describe membrane-bound and soluble factors, their regulation, and their impact on immune cell activation in the TME. Furthermore, we give an overview of the tumor/antigen presentation and how it is influenced under malignant conditions. Finally, we summarize novel TME-targeting agents, which are already in clinical trials for different tumor entities.

scholarly journals Immune Evasion Mechanism and AXL

2021 ◽  
Vol 11 ◽  
Author(s):  
Hye-Youn Son ◽  
Hwan-Kyu Jeong
Keyword(s):  
Tumor Microenvironment ◽  
Immune Responses ◽  
Signaling Pathway ◽  
Immune Evasion ◽  
Cell Activation ◽  
Immune Cell ◽  
Nk Cell ◽  
Multiple Cancer ◽  
Clinical Prognosis ◽  
Programmed Death

Extensive interest in cancer immunotherapy is reported according to the clinical importance of CTLA-4 and (PD-1/PD-L1) [programmed death (PD) and programmed death-ligand (PD-L1)] in immune checkpoint therapies. AXL is a receptor tyrosine kinase expressed in different types of cancer and in relation to resistance against various anticancer therapeutics due to poor clinical prognosis. AXL and its ligand, i.e., growth arrest-specific 6 (GAS6) proteins, are expressed on many cancer cells, and the GAS6/AXL pathway is reported to promote cancer cell proliferation, survival, migration, invasion, angiogenesis, and immune evasion. AXL is an attractive and novel therapeutic target for impairing tumor progression from immune cell contracts in the tumor microenvironment. The GAS6/AXL pathway is also of interest immunologically because it targets fewer antitumor immune responses. In effect, several targeted therapies are selective and nonselective for AXL, which are in preclinical and clinical development in multiple cancer types. Therefore, this review focuses on the role of the GAS6/AXL signaling pathway in triggering the immunosuppressive tumor microenvironment as immune evasion. This includes regulating its composition and activating T-cell exclusion with the immune-suppressive activity of regulatory T cells, which is related to one of the hallmarks of cancer survival. Finally, this article discusses the GAS6/AXL signaling pathway in the context of several immune responses such as NK cell activation, apoptosis, and tumor-specific immunity, especially PD-1/PDL-1 signaling.

438 Synergy between SEA-CD40 and chemotherapeutics drives curative antitumor activity in preclinical models

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A464-A464
Author(s):  
Weiping Zeng ◽  
Haley Neff-LaFord ◽  
Sahar Ansari ◽  
Celine Jacquemont ◽  
Michael Schmitt ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Death ◽  
Tumor Microenvironment ◽  
Antitumor Activity ◽  
Cell Activation ◽  
Tumor Antigens ◽  
Immune Cell ◽  
Chemotherapeutic Agents ◽  
Clinical Development ◽  
Immune Cell Activation

BackgroundCD40 is a co-stimulatory receptor of the TNF receptor superfamily expressed on antigen presenting cells (APCs). Antibodies targeting CD40 may have antitumor therapeutic benefit by driving innate immune cell activation that supports generation of antigen-specific T cell responses. Multiple CD40-directed antibodies are in clinical development in both solid and hematologic indications and differ according to immunoglobulin isotype, affinity to CD40, and differential FcγR-binding. SEA-CD40 is an agonistic nonfucosylated, humanized IgG1 monoclonal antibody directed against CD40. SEA-CD40 is distinct from other CD40 targeted agents in clinical development as it binds with increased affinity to FcγRIIIa resulting in enhanced effector function and CD40 agonism. This unique composition of SEA-CD40 could amplify immune stimulation and antitumor activity relative to other CD40-directed therapeutics.MethodsEffective immunity requires the presence of diverse antigens to drive generation of distinct antigen-specific memory T cells. SEA-CD40 in many ways works like a vaccine as it can increase active acquired immunity against endogenous tumor antigens. A potential limiting factor for maximal SEA-CD40 antitumor activity across multiple tumor types may be the limited level and diversity of tumor-associated antigens within the tumor microenvironment (TME). Chemotherapeutic agents drive tumor cell death resulting in the release and increase of tumor antigens locally within the TME. Combining chemotherapeutic agents with SEA-CD40 could facilitate robust antigen release and amplified presentation of those antigens to CD8+ T cells. Antitumor activity and immune cell changes of SEA-CD40 in combination with chemotherapeutic agents was evaluated in vitro and in vivo using human CD40 transgenic mice.ResultsIn preclinical mouse models, SEA-CD40 combined with chemotherapeutic agents to drive robust anti-tumor activity. The nature of the chemotherapeutic agent influenced immune cell activation within the tumor microenvironment (TME) and extent of combinability with SEA-CD40. Preclinical assessment indicates that chemotherapeutics which induce immunogenic cell death (ICD) combine with SEA-CD40 to increase curative activity compared to non-ICD-inducing chemotherapeutics. The preferred partnership of SEA-CD40 with ICD-inducing agents, such as a monomethyl auristatin E (MMAE) antibody-drug conjugate, increased curative antitumor activity in mouse models. The combination of SEA-CD40 and chemotherapeutic agents with a T cell targeted anti-PD1 antibody could deepen and extend these anti-tumor responses.ConclusionsThese data support continued clinical evaluation of SEA-CD40 in combination with chemotherapeutic agents and potentially in the future MMAE based ADCs. A phase 1 clinical trial is actively enrolling (NCT02376699) and includes a cohort in pancreatic cancer assessing the combination of SEA-CD40, gemcitabine, nab-paclitaxel, and pembrolizumab.Ethics ApprovalStudies with human samples were performed according to institutional ethics standards. Animals studies were approved by and conducted in accordance with Seattle Genetics Institutional Care and Use Committee protocol #SGE-029.

scholarly journals Mechanoimmunology: molecular-scale forces govern immune cell functions

2018 ◽  
Vol 29 (16) ◽  
pp. 1919-1926 ◽  
Author(s):  
Sophie V. Pageon ◽  
Matt A. Govendir ◽  
Daryan Kempe ◽  
Maté Biro
Keyword(s):  
Immune Responses ◽  
Cell Activation ◽  
Immune Cell ◽  
Imaging Techniques ◽  
Mechanical Forces ◽  
The Novel ◽  
Cell Functions ◽  
Immune Cell Activation ◽  
Receptor Interactions

Immune cell recognition of antigens is a pivotal process in initiating immune responses against injury, pathogens, and cancers. Breakthroughs over the past decade support a major role for mechanical forces in immune responses, laying the foundation for the emerging field of mechanoimmunology. In this Perspective, we discuss the mechanical forces acting at the level of ligand–receptor interactions and how they underpin receptor triggering, signal initiation, and immune cell activation. We also highlight the novel biophysical tools and advanced imaging techniques that have afforded us the recent progress in our understanding of the role of forces in immune cell functions.

scholarly journals Fatty acids and immune function: new insights into mechanisms

2007 ◽  
Vol 98 (S1) ◽  
pp. S41-S45 ◽  
Author(s):  
Parveen Yaqoob ◽  
Philip C. Calder
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Immune Responses ◽  
Cell Activation ◽  
Inflammatory Mediator ◽  
Immune Cell ◽  
Structural Components ◽  
Immune Cell Activation ◽  
Cell Responses ◽  
Inflammatory Mediator Production

Fatty acids are known to play diverse roles in immune cells. They are important as a source of energy, as structural components of cell membranes, as signaling molecules and as precursors for the synthesis of eicosanoids and similar mediators. Recent research has suggested that the localization and organisation of fatty acids into distinct cellular pools has a direct influence on the behaviour of a number of proteins involved in immune cell activation, including those associated with T cell responses, antigen presentation and fatty acid-derived inflammatory mediator production. This article reviews these studies and places them in the context of existing literature in the field. These studies indicate the existence of several novel mechanisms by which altered fatty acid availability can modulate immune responses and impact upon clinical outcomes.

scholarly journals Overview of Immunological Responses and Immunomodulation Properties of Trichuris sp.: Prospects for Better Understanding Human Trichuriasis

Life ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 188
Author(s):  
Dewi Masyithah Darlan ◽  
Muhammad Fakhrur Rozi ◽  
Hemma Yulfi
Keyword(s):  
Immune Responses ◽  
Cell Activation ◽  
Immune Cell ◽  
Inflammatory Responses ◽  
Cell Polarization ◽  
Innate Immune Responses ◽  
Immunological Responses ◽  
Novel Treatments ◽  
Immune Cell Activation ◽  
Bowel Diseases

Trichuris sp. infection has appeared as a pathological burden in the population, but the immunomodulation features could result in an opportunity to discover novel treatments for diseases with prominent inflammatory responses. Regarding the immunological aspects, the innate immune responses against Trichuris sp. are also responsible for determining subsequent immune responses, including the activation of innate lymphoid cell type 2 (ILC2s), and encouraging the immune cell polarization of the resistant host phenotype. Nevertheless, this parasite can establish a supportive niche for worm survival and finally avoid host immune interference. Trichuris sp. could skew antigen recognition and immune cell activation and proliferation through the generation of specific substances, called excretory/secretory (ESPs) and soluble products (SPs), which mainly mediate its immunomodulation properties. Through this review, we elaborate and discuss innate–adaptive immune responses and immunomodulation aspects, as well as the clinical implications for managing inflammatory-based diseases, such as inflammatory bowel diseases, allergic, sepsis, and other autoimmune diseases.

Oxidized Haemoglobin–Driven Endothelial Dysfunction and Immune Cell Activation: Novel Therapeutic Targets for Atherosclerosis

2013 ◽  
Vol 20 (37) ◽  
pp. 4806-4814 ◽  
Author(s):  
Brigitta Buttari ◽  
Elisabetta Profumo ◽  
Rita Businaro ◽  
Luciano Saso ◽  
Raffaele Capoano ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Cell Activation ◽  
Immune Cell ◽  
Therapeutic Targets ◽  
Immune Cell Activation ◽  
Novel Therapeutic

scholarly journals Neuronal guidance proteins in cardiovascular inflammation

2021 ◽  
Vol 116 (1) ◽  
Author(s):  
Marius Keller ◽  
Valbona Mirakaj ◽  
Michael Koeppen ◽  
Peter Rosenberger
Keyword(s):  
Cell Activation ◽  
Immune Cell ◽  
Vascular Endothelial ◽  
Therapeutic Approaches ◽  
Immune Cell Activation ◽  
Cytokines And Chemokines ◽  
The Future ◽  
Cardiovascular Pathologies ◽  
Neuronal Guidance

AbstractCardiovascular pathologies are often induced by inflammation. The associated changes in the inflammatory response influence vascular endothelial biology; they complicate the extent of ischaemia and reperfusion injury, direct the migration of immune competent cells and activate platelets. The initiation and progression of inflammation is regulated by the classical paradigm through the system of cytokines and chemokines. Therapeutic approaches have previously used this knowledge to control the extent of cardiovascular changes with varying degrees of success. Neuronal guidance proteins (NGPs) have emerged in recent years and have been shown to be significantly involved in the control of tissue inflammation and the mechanisms of immune cell activation. Therefore, proteins of this class might be used in the future as targets to control the extent of inflammation in the cardiovascular system. In this review, we describe the role of NGPs during cardiovascular inflammation and highlight potential therapeutic options that could be explored in the future.

scholarly journals Oxidative stress and immune cell activation quantification in sepsis and non-sepsis critical care patients by neopterin/7,8-dihydroneopterin analysis

Pteridines ◽  
2020 ◽  
Vol 31 (1) ◽  
pp. 68-82
Author(s):  
Gregory Baxter-Parker ◽  
Ravinder Reddy Gaddam ◽  
Elena Moltchanova ◽  
Anitra Carr ◽  
Geoff Shaw ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Kidney Function ◽  
Cell Activation ◽  
Immune Cell ◽  
Intensive Care Patients ◽  
Immune Cell Activation ◽  
Immune System Activation ◽  
System Activation ◽  
Urinary Neopterin ◽  
Critical Care Patients

AbstractIntroduction: Neopterin and 7,8-dihydroneopterin are used as biomarkers of oxidative stress and inflammation, but the effect of kidney function on these measurements has not been extensively explored. We examine the levels of oxidative stress, inflammation and kidney function in intensive patients and compare them to equivalent patients without sepsis.Methods: 34 Intensive care patients were selected for the study, 14 without sepsis and 20 with. Both groups had equivalent levels of trauma, assessed by SAPS II, SOFA, and APACHE II and III scores. Plasma and urinary neopterin and total neopterin (neopterin + 7,8-dihydroneopterin) values were measured.Results: Neopterin and total neopterin were significantly elevated in urine and plasma for multiple days in sepsis versus non-sepsis patients. Plasma neopterin and total neopterin have decreasing relationships with increased eGFR (p<0.008 and p<0.001, respectively). Plasma/urinary neopterin and total neopterin ratios demonstrate that total neopterin flux is more influenced by eGFR than neopterin, with significantce of p<0.02 and p<0.0002 respectively.Conclusion: Sepsis patients present with greater levels of oxidative stress and immune system activation than non-sepsis patients of equal levels of trauma, as measured by neopterin and total neopterin. eGFR may need to be taken into account when accessing the level of inflammation from urinary neopterin measurements.

scholarly journals RhoA Signaling in Immune Cell Response and Cardiac Disease

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1681
Author(s):  
Lucia Sophie Kilian ◽  
Derk Frank ◽  
Ashraf Yusuf Rangrez
Keyword(s):  
Cardiac Disease ◽  
Cell Response ◽  
Cell Activation ◽  
Immune Cell ◽  
Inflammatory Diseases ◽  
Heart Diseases ◽  
Small Gtpase ◽  
Cardiac Inflammation ◽  
Immune Cell Activation ◽  
Immune Cell Response

Chronic inflammation, the activation of immune cells and their cross-talk with cardiomyocytes in the pathogenesis and progression of heart diseases has long been overlooked. However, with the latest research developments, it is increasingly accepted that a vicious cycle exists where cardiomyocytes release cardiocrine signaling molecules that spiral down to immune cell activation and chronic state of low-level inflammation. For example, cardiocrine molecules released from injured or stressed cardiomyocytes can stimulate macrophages, dendritic cells, neutrophils and even T-cells, which then subsequently increase cardiac inflammation by co-stimulation and positive feedback loops. One of the key proteins involved in stress-mediated cardiomyocyte signal transduction is a small GTPase RhoA. Importantly, the regulation of RhoA activation is critical for effective immune cell response and is being considered as one of the potential therapeutic targets in many immune-cell-mediated inflammatory diseases. In this review we provide an update on the role of RhoA at the juncture of immune cell activation, inflammation and cardiac disease.

scholarly journals Hybrid Nanoassemblies from Viruses and DNA Nanostructures

Nanomaterials ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1413
Author(s):  
Sofia Ojasalo ◽  
Petteri Piskunen ◽  
Boxuan Shen ◽  
Mauri A. Kostiainen ◽  
Veikko Linko
Keyword(s):  
Cell Activation ◽  
Immune Cell ◽  
Dna Nanotechnology ◽  
Biological Properties ◽  
Dna Nanostructures ◽  
Dna Structures ◽  
Nanoscale Structures ◽  
Immune Cell Activation ◽  
Wide Range ◽  
Structural Dna Nanotechnology

Viruses are among the most intriguing nanostructures found in nature. Their atomically precise shapes and unique biological properties, especially in protecting and transferring genetic information, have enabled a plethora of biomedical applications. On the other hand, structural DNA nanotechnology has recently emerged as a highly useful tool to create programmable nanoscale structures. They can be extended to user defined devices to exhibit a wide range of static, as well as dynamic functions. In this review, we feature the recent development of virus-DNA hybrid materials. Such structures exhibit the best features of both worlds by combining the biological properties of viruses with the highly controlled assembly properties of DNA. We present how the DNA shapes can act as “structured” genomic material and direct the formation of virus capsid proteins or be encapsulated inside symmetrical capsids. Tobacco mosaic virus-DNA hybrids are discussed as the examples of dynamic systems and directed formation of conjugates. Finally, we highlight virus-mimicking approaches based on lipid- and protein-coated DNA structures that may elicit enhanced stability, immunocompatibility and delivery properties. This development also paves the way for DNA-based vaccines as the programmable nano-objects can be used for controlling immune cell activation.

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