Current Adenosinergic Therapies: What Do Cancer Cells Stand to Gain and Lose?

A key objective in immuno-oncology is to reactivate the dormant immune system and increase tumour immunogenicity. Adenosine is an omnipresent purine that is formed in response to stress stimuli in order to restore physiological balance, mainly via anti-inflammatory, tissue-protective, and anti-nociceptive mechanisms. Adenosine overproduction occurs in all stages of tumorigenesis, from the initial inflammation/local tissue damage to the precancerous niche and the developed tumour, making the adenosinergic pathway an attractive but challenging therapeutic target. Many current efforts in immuno-oncology are focused on restoring immunosurveillance, largely by blocking adenosine-producing enzymes in the tumour microenvironment (TME) and adenosine receptors on immune cells either alone or combined with chemotherapy and/or immunotherapy. However, the effects of adenosinergic immunotherapy are not restricted to immune cells; other cells in the TME including cancer and stromal cells are also affected. Here we summarise recent advancements in the understanding of the tumour adenosinergic system and highlight the impact of current and prospective immunomodulatory therapies on other cell types within the TME, focusing on adenosine receptors in tumour cells. In addition, we evaluate the structure- and context-related limitations of targeting this pathway and highlight avenues that could possibly be exploited in future adenosinergic therapies.

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New Roads Open Up for Implementing Immunotherapy in Mesothelioma

Clinical and Developmental Immunology ◽

10.1155/2012/927240 ◽

2012 ◽

Vol 2012 ◽

pp. 1-13 ◽

Cited By ~ 13

Author(s):

R. Cornelissen ◽

M. E. Heuvers ◽

A. P. Maat ◽

R. W. Hendriks ◽

H. C. Hoogsteden ◽

...

Keyword(s):

Immune System ◽

Immune Cells ◽

Tumour Growth ◽

Treatment Options ◽

Cell Types ◽

Tumour Microenvironment ◽

Evidence Based ◽

Evidence Based Treatment ◽

Good Clinical Condition ◽

Defence Strategies

Treatment options for malignant mesothelioma are limited, and the results with conventional therapies have been rather disappointing to this date. Chemotherapy is the only evidence-based treatment for mesothelioma patients in good clinical condition, with an increase in median survival of only 2 months. Therefore, there is urgent need for a different approach to battle this malignancy. As chronic inflammation precedes mesothelioma, the immune system plays a key role in the initiation of this type of tumour. Also, many immunological cell types can be found within the tumour at different stages of the disease. However, mesothelioma cells can evade the surveillance capacity of the immune system. They build a protective tumour microenvironment to harness themselves against the immune system's attacks, in which they even abuse immune cells to act against the antitumour immune response. In our opinion, modulating the immune system simultaneously with the targeting of mesothelioma tumour cells might prove to be a superior treatment. However, this strategy is challenging since the tumour microenvironment possesses numerous forms of defence strategies. In this paper, we will discuss the interplay between immunological cells that can either inhibit or stimulate tumour growth and the challenges associated with immunotherapy. We will provide possible strategies and discuss opportunities to overcome these problems.

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Uncovering the Diversification of Tissue Engineering on the Emergent Areas of Stem Cells, Nanotechnology and Biomaterials

Current Stem Cell Research & Therapy ◽

10.2174/1574888x15666200103124821 ◽

2020 ◽

Vol 15 (3) ◽

pp. 187-201 ◽

Cited By ~ 1

Author(s):

Sunil K. Dubey ◽

Amit Alexander ◽

Munnangi Sivaram ◽

Mukta Agrawal ◽

Gautam Singhvi ◽

...

Keyword(s):

Tissue Engineering ◽

Stem Cells ◽

Immune System ◽

Clinical Application ◽

Cell Types ◽

Patient Specific ◽

Potential Strategy ◽

Induced Pluripotent ◽

Treat All ◽

The Impact

Damaged or disabled tissue is life-threatening due to the lack of proper treatment. Many conventional transplantation methods like autograft, iso-graft and allograft are in existence for ages, but they are not sufficient to treat all types of tissue or organ damages. Stem cells, with their unique capabilities like self-renewal and differentiate into various cell types, can be a potential strategy for tissue regeneration. However, the challenges like reproducibility, uncontrolled propagation and differentiation, isolation of specific kinds of cell and tumorigenic nature made these stem cells away from clinical application. Today, various types of stem cells like embryonic, fetal or gestational tissue, mesenchymal and induced-pluripotent stem cells are under investigation for their clinical application. Tissue engineering helps in configuring the stem cells to develop into a desired viable tissue, to use them clinically as a substitute for the conventional method. The use of stem cell-derived Extracellular Vesicles (EVs) is being studied to replace the stem cells, which decreases the immunological complications associated with the direct administration of stem cells. Tissue engineering also investigates various biomaterials to use clinically, either to replace the bones or as a scaffold to support the growth of stemcells/ tissue. Depending upon the need, there are various biomaterials like bio-ceramics, natural and synthetic biodegradable polymers to support replacement or regeneration of tissue. Like the other fields of science, tissue engineering is also incorporating the nanotechnology to develop nano-scaffolds to provide and support the growth of stem cells with an environment mimicking the Extracellular matrix (ECM) of the desired tissue. Tissue engineering is also used in the modulation of the immune system by using patient-specific Mesenchymal Stem Cells (MSCs) and by modifying the physical features of scaffolds that may provoke the immune system. This review describes the use of various stem cells, biomaterials and the impact of nanotechnology in regenerative medicine.

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

Frontiers in Molecular Neuroscience ◽

10.3389/fnmol.2021.767041 ◽

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.

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Nutritional immunity: the impact of metals on lung immune cells and the airway microbiome during chronic respiratory disease

Respiratory Research ◽

10.1186/s12931-021-01722-y ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Claire Healy ◽

Natalia Munoz-Wolf ◽

Janné Strydom ◽

Lynne Faherty ◽

Niamh C. Williams ◽

...

Keyword(s):

Immune System ◽

Trace Metals ◽

Lung Disease ◽

Chronic Lung Disease ◽

Immune Cells ◽

Immune Cell ◽

Redox Activity ◽

Nutritional Immunity ◽

Airway Microbiome ◽

The Impact

AbstractNutritional immunity is the sequestration of bioavailable trace metals such as iron, zinc and copper by the host to limit pathogenicity by invading microorganisms. As one of the most conserved activities of the innate immune system, limiting the availability of free trace metals by cells of the immune system serves not only to conceal these vital nutrients from invading bacteria but also operates to tightly regulate host immune cell responses and function. In the setting of chronic lung disease, the regulation of trace metals by the host is often disrupted, leading to the altered availability of these nutrients to commensal and invading opportunistic pathogenic microbes. Similarly, alterations in the uptake, secretion, turnover and redox activity of these vitally important metals has significant repercussions for immune cell function including the response to and resolution of infection. This review will discuss the intricate role of nutritional immunity in host immune cells of the lung and how changes in this fundamental process as a result of chronic lung disease may alter the airway microbiome, disease progression and the response to infection.

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Differences in DNA methylation of white blood cell types at birth and in adulthood reflect postnatal immune maturation and influence accuracy of cell type prediction

10.1101/399279 ◽

2018 ◽

Cited By ~ 3

Author(s):

Meaghan J Jones ◽

Louie Dinh ◽

Hamid Reza Razzaghian ◽

Olivia de Goede ◽

Julia L MacIsaac ◽

...

Keyword(s):

Dna Methylation ◽

Immune System ◽

Blood Cell ◽

Cord Blood ◽

White Blood Cell ◽

Blood Cells ◽

Cell Types ◽

Cell Type ◽

Cell Type Specific ◽

The Impact

AbstractBackgroundDNA methylation profiling of peripheral blood leukocytes has many research applications, and characterizing the changes in DNA methylation of specific white blood cell types between newborn and adult could add insight into the maturation of the immune system. As a consequence of developmental changes, DNA methylation profiles derived from adult white blood cells are poor references for prediction of cord blood cell types from DNA methylation data. We thus examined cell-type specific differences in DNA methylation in leukocyte subsets between cord and adult blood, and assessed the impact of these differences on prediction of cell types in cord blood.ResultsThough all cell types showed differences between cord and adult blood, some specific patterns stood out that reflected how the immune system changes after birth. In cord blood, lymphoid cells showed less variability than in adult, potentially demonstrating their naïve status. In fact, cord CD4 and CD8 T cells were so similar that genetic effects on DNA methylation were greater than cell type effects in our analysis, and CD8 T cell frequencies remained difficult to predict, even after optimizing the library used for cord blood composition estimation. Myeloid cells showed fewer changes between cord and adult and also less variability, with monocytes showing the fewest sites of DNA methylation change between cord and adult. Finally, including nucleated red blood cells in the reference library was necessary for accurate cell type predictions in cord blood.ConclusionChanges in DNA methylation with age were highly cell type specific, and those differences paralleled what is known about the maturation of the postnatal immune system.

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Crosstalk between Red Blood Cells and the Immune System and Its Impact on Atherosclerosis

BioMed Research International ◽

10.1155/2015/616834 ◽

2015 ◽

Vol 2015 ◽

pp. 1-8 ◽

Cited By ~ 34

Author(s):

Brigitta Buttari ◽

Elisabetta Profumo ◽

Rachele Riganò

Keyword(s):

Oxidative Stress ◽

Immune System ◽

Red Blood Cells ◽

Immune Cells ◽

Blood Cells ◽

Atherosclerotic Disease ◽

Intraplaque Hemorrhage ◽

Immune System Activation ◽

Adaptive Immune Cells ◽

The Impact

Atherosclerosis is a chronic multifactorial disease of the arterial wall characterized by inflammation, oxidative stress, and immune system activation. Evidence exists on a pathogenic role of oxidized red blood cells (RBCs) accumulated in the lesion after intraplaque hemorrhage. This review reports current knowledge on the impact of oxidative stress in RBC modifications with the surface appearance of senescent signals characterized by reduced expression of CD47 and glycophorin A and higher externalization of phosphatidylserine. The review summarizes findings indicating that oxidized, senescent, or stored RBCs, due to surface antigen modification and release of prooxidant and proinflammatory molecules, exert an impaired modulatory activity on innate and adaptive immune cells and how this activity contributes to atherosclerotic disease. In particular RBCs from patients with atherosclerosis, unlike those from healthy subjects, fail to control lipopolysaccharide-induced DC maturation and T lymphocyte apoptosis. Stored RBCs, accompanied by shedding of extracellular vesicles, stimulate peripheral blood mononuclear cells to release proinflammatory cytokines, augment mitogen-driven T cell proliferation, and polarize macrophages toward the proinflammatory M1 activation pathway. Collectively, literature data suggest that the crosstalk between RBCs with immune cells represents a novel mechanism by which oxidative stress can contribute to atherosclerotic disease progression and may be exploited for therapeutic interventions.

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The impact of host immune cells on the development of neurofibromatosis type 1: The abnormal immune system provides an immune microenvironment for tumorigenesis

Neuro-Oncology Advances ◽

10.1093/noajnl/vdz037 ◽

2019 ◽

Vol 2 (Supplement_1) ◽

pp. i33-i39

Author(s):

Cheng-Jiang Wei ◽

Shu-Chen Gu ◽

Jie-Yi Ren ◽

Yi-Hui Gu ◽

Xiang-Wen Xu ◽

...

Keyword(s):

Immune System ◽

Immune Cells ◽

Neurofibromatosis Type 1 ◽

Immune Escape ◽

Genetic Disorder ◽

Neurofibromatosis Type ◽

Complex Interactions ◽

Nf1 Gene ◽

The Impact

Abstract AbstractThe immune system plays an essential role in the development of tumors, which has been demonstrated in multiple types of cancers. Consistent with this, immunotherapies with targets that disrupt these mechanisms and turn the immune system against developing cancers have been proven effective. In neurofibromatosis type 1 (NF1), an autosomal dominant genetic disorder, the understanding of the complex interactions of the immune system is incomplete despite the discovery of the pivotal role of immune cells in the tumor microenvironment. Individuals with NF1 show a loss of the NF1 gene in nonneoplastic cells, including immune cells, and the aberrant immune system exhibits intriguing interactions with NF1. This review aims to provide an update on recent studies showing the bilateral influences of NF1 mutations on immune cells and how the abnormal immune system promotes the development of NF1 and NF1-related tumors. We then discuss the immune receptors major histocompatibility complex class I and II and the PD-L1 mechanism that shield NF1 from immunosurveillance and enable the immune escape of tumor tissues. Clarification of the latest understanding of the mechanisms underlying the effects of the abnormal immune system on promoting the development of NF1 will indicate potential future directions for further studies and new immunotherapies.

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Interaction of allogeneic adipose tissue-derived stromal cells and unstimulated immune cells in vitro: the impact of cell-to-cell contact and hypoxia in the local milieu

Cytotechnology ◽

10.1007/s10616-017-0144-x ◽

2017 ◽

Vol 70 (1) ◽

pp. 299-312 ◽

Cited By ~ 4

Author(s):

Aleksandra N. Gornostaeva ◽

Elena R. Andreeva ◽

Polina I. Bobyleva ◽

Ludmila B. Buravkova

Keyword(s):

Adipose Tissue ◽

Immune Cells ◽

Stromal Cells ◽

Cell Contact ◽

The Impact

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The Impact of Ghrelin in Metabolic Diseases: An Immune Perspective

Journal of Diabetes Research ◽

10.1155/2017/4527980 ◽

2017 ◽

Vol 2017 ◽

pp. 1-15 ◽

Cited By ~ 20

Author(s):

Jéssica Aparecida da Silva Pereira ◽

Felipe Corrêa da Silva ◽

Pedro Manoel Mendes de Moraes-Vieira

Keyword(s):

Immune Cells ◽

Metabolic Diseases ◽

Inflammatory Diseases ◽

Cell Types ◽

Low Grade ◽

Growth Hormone Secretagogue Receptor ◽

Growth Hormone Secretagogue ◽

Increased Risk ◽

Inflammatory Profile ◽

The Impact

Obesity and insulin resistance have reached epidemic proportions. Obesogenic conditions are associated with increased risk for the development of other comorbidities and obesity-related diseases. In metabolic disorders, there is chronic low-grade inflammation induced by the activation of immune cells, especially in metabolic relevant organs such as white adipose tissue (WAT). These immune cells are regulated by environmental and systemic cues. Ghrelin is a peptide secreted mainly by X/A-like gastric cells and acts through the growth hormone secretagogue receptor (GHS-R). This receptor is broadly expressed in the central nervous system (CNS) and in several cell types, including immune cells. Studies show that ghrelin induces an orexigenic state, and there is increasing evidence implicating an immunoregulatory role for ghrelin. Ghrelin mainly acts on the innate and adaptive immune systems to suppress inflammation and induce an anti-inflammatory profile. In this review, we discuss the immunoregulatory roles of ghrelin, the mechanisms by which ghrelin acts and potential pharmacological applications for ghrelin in the treatment of obesity-associated inflammatory diseases, such as type 2 diabetes (T2D).

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

10.5772/intechopen.98617 ◽

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.

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