Hormone-Related Cancer and Autoimmune Diseases: A Complex Interplay to be Discovered

Neoplasic transformation is a continuous process that occurs in the body. Even before clinical signs, the immune system is capable of recognizing these aberrant cells and reacting to suppress them. However, transformed cells acquire the ability to evade innate and adaptive immune defenses through the secretion of molecules that inhibit immune effector functions, resulting in tumor progression. Hormones have the ability to modulate the immune system and are involved in the pathogenesis of autoimmune diseases, and cancer. Hormones can control both the innate and adaptive immune systems in men and women. For example androgens reduce immunity through modulating the production of pro-inflammatory and anti-inflammatory mediators. Women are more prone than men to suffer from autoimmune diseases such as systemic lupus erythematosus, psoriasis and others. This is linked to female hormones modulating the immune system. Patients with autoimmune diseases consistently have an increased risk of cancer, either as a result of underlying immune system dysregulation or as a side effect of pharmaceutical treatments. Epidemiological data on cancer incidence emphasize the link between the immune system and cancer. We outline and illustrate the occurrence of hormone-related cancer and its relationship to the immune system or autoimmune diseases in this review. It is obvious that some observations are contentious and require explanation of molecular mechanisms and validation. As a result, future research should clarify the molecular pathways involved, including any causal relationships, in order to eventually allocate information that will aid in the treatment of hormone-sensitive cancer and autoimmune illness.

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Hormonal Contraception and the Development of Autoimmunity: A Review of the Literature

The Linacre Quarterly ◽

10.1080/00243639.2017.1360065 ◽

2017 ◽

Vol 84 (3) ◽

pp. 275-295 ◽

Cited By ~ 7

Author(s):

William V. Williams

Keyword(s):

Crohn’S Disease ◽

Immune System ◽

Crohn's Disease ◽

Autoimmune Diseases ◽

Interstitial Cystitis ◽

White Blood Cells ◽

The Body ◽

Hormonal Contraceptives ◽

Chemical Components ◽

Increased Risk

Estrogens and progestins are known to have profound effects on the immune system and may modulate the susceptibility to autoimmune diseases. A comprehensive literature search was carried out using PubMed for any of 153 autoimmune disease terms and the terms contraception, contraceptive, or their chemical components with limits of Humans + Title or Abstract. Over 1,800 titles were returned and scanned, 352 papers retrieved and reviewed in depth and an additional 70 papers retrieved from the bibliographies. Based on this review, substantial evidence exists linking the use of combined oral contraceptives to a lower incidence of hyperthyroidism, an increase in multiple sclerosis, ulcerative colitis, Crohn's disease, Systemic Lupus Erythematosus, and interstitial cystitis. Progesterone only contraceptives are linked to progesterone dermatitis and in one large developing world concurrent cohort study are associated with increases in arthropathies and related disorders, eczema and contact dermatitis, pruritis and related conditions, alopecia, acne, and urticaria. Hormonal contraceptives modulate the immune system and may influence the susceptibility to autoimmune diseases with significant increases in risk for several autoimmune diseases. Summary Hormonal contraceptives (HCs), such as the “pill,” Norplant, and vaginal rings, are very potent hormones that have effects on the immune system, which is made up of white blood cells and lymph nodes and normally defends the body against invading bacteria, viruses and parasites. This review looked at the association of HC use to the development of autoimmune diseases, where the immune system turns against the body and causes damage to organs. There is good evidence that HC use is associated with an increased risk of several serious autoimmune diseases such as Crohn's disease (which causes inflammation of the bowels), Lupus (which causes inflammation in many organs), and interstitial cystitis (which causes inflammation in the bladder). Several other rarer autoimmune diseases are also linked to HC use. People contemplating the use of HCs should be informed of these risks.

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Involvement of Probiotics and Postbiotics in the Immune System Modulation

Biologics ◽

10.3390/biologics1020006 ◽

2021 ◽

Vol 1 (2) ◽

pp. 89-110

Author(s):

Neslihan Yeşilyurt ◽

Birsen Yılmaz ◽

Duygu Ağagündüz ◽

Raffaele Capasso

Keyword(s):

Immune System ◽

Pharmaceutical Industry ◽

Intestinal Microbiota ◽

Health Benefits ◽

The Body ◽

Future Research ◽

Immune Systems ◽

Advantages And Disadvantages ◽

Immune System Modulation ◽

Molecular Patterns

Intestinal microbiota interacts with other systems, especially the immune system, which is responsible for protecting the body by recognizing “stranger” (pathogen associated molecular patterns-PAMPs) and “danger” (damage-associated molecular patterns-DAMPs) molecular motifs. In this manner, it plays an important role in the pathogenesis of various diseases and health. Despite the use of probiotics that modulate the intestinal microbiota in providing health benefits and in the treatment of diseases, there are some possible concerns about the possibility of developing adverse effects, especially in people with suppressed immune systems. Since probiotics provide health benefits with bioactive compounds, studies are carried out on the use of products containing non-living probiotic microorganisms (paraprobiotics) and/or their metabolites (postbiotics) instead of probiotic products. It is even reported that these microbial compounds have more immunomodulatory activities than living microorganisms via some possible mechanism and eliminates some disadvantages of probiotics. Considering the increasing use of functional foods in health and disease, further studies are needed with respect to the benefits and advantages of parabiotic and/or postbiotic use in the food and pharmaceutical industry as well as immune system modulation. Although probiotics have been extensive studied for a long time, it seems that postbiotics are promising tools for future research and applications according to the recent literature. This review aimed to evaluate the interaction of probiotics and postbiotics with the immune systems and also their advantages and disadvantages in the area of food-pharmaceutical industry and immune system modulation.

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Human papillomavirus-driven immune deviation: challenge and novel opportunity for immunotherapy

Therapeutic Advances in Vaccines ◽

10.1177/2051013617717914 ◽

2017 ◽

Vol 5 (3) ◽

pp. 69-82 ◽

Cited By ~ 25

Author(s):

Sigrun Smola ◽

Connie Trimble ◽

Peter L. Stern

Keyword(s):

Human Papillomavirus ◽

Immune System ◽

Immune Escape ◽

Hpv Vaccination ◽

Suppressor Cells ◽

Clinical Problem ◽

Hpv Infection ◽

Treatment Protocols ◽

Increased Risk ◽

Risk Of Cancer

It is now recognized that the immune system can be a key component of restraint and control during the neoplastic process. Human papillomavirus (HPV)-associated cancers of the anogenital tract and oropharynx represent a significant clinical problem but there is a clear opportunity for immune targeting of the viral oncogene expression that drives cancer development. However, high-risk HPV infection of the target epithelium and the expression of the E6/E7 oncogenes can lead to early compromise of the innate immune system (loss of antigen-presenting cells) facilitating viral persistence and increased risk of cancer. In these circumstances, a succession of interacting and self-reinforcing events mediated through modulation of different immune receptors, chemokine and cytokine responses (CCL20; CCL2; CCR2; IL-6; CCR7; IL-12) further promote the generation of an immune suppressive microenvironment [increased levels of Tregs, Th17, myeloid-derived suppressor cells (MDSCs) and PD-L1]. The overexpression of E6/E7 expression also compromises the ability to repair cellular DNA, leading to genomic instability, with the acquisition of genetic changes providing for the selection of advantaged cancer cells including additional strategies for immune escape. Therapeutic vaccines targeting the HPV oncogenes have shown some encouraging success in some recent early-phase clinical trials tested in patients with HPV-associated high-grade anogenital lesions. A significant hurdle to success in more advanced disease will be the local and systemic immune suppressive factors. Interventions targeting the different immunosuppressive components can provide opportunity to release existing or generate new and effective antitumour immunity. Treatments that alter the protumour inflammatory environment including toll-like receptor stimulation, inhibition of IL-6-related pathways, immune-checkpoint inhibition, direct modulation of MDSCs, Tregs and macrophages could all be useful in combination with therapeutic HPV vaccination. Future progress in delivering successful immunotherapy will depend on the configuration of treatment protocols in an insightful and timely combination.

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Mechanisms of the induction of autoimmunity

Srpski arhiv za celokupno lekarstvo ◽

10.2298/sarh05s1009m ◽

2005 ◽

Vol 133 (Suppl. 1) ◽

pp. 9-15 ◽

Cited By ~ 2

Author(s):

Marija Mostarica-Stojkovic

Keyword(s):

Immune System ◽

T Cell ◽

Autoimmune Diseases ◽

Molecular Mimicry ◽

The Body ◽

Peripheral Tolerance ◽

High Avidity ◽

Main Function ◽

Clonal Deletion ◽

Genetic Traits

The main function of the immune system is to protect the body by responding to invading microorganisms. Immunologic tolerance is the basic property of the immune system that provides for self/non-self discrimination so that the immune system can protect the host from external pathogens without reacting against itself. Central tolerance is achieved by the clonal deletion of self-reactive lymphocytes expressing receptors with high avidity for self. Autoreactive lymphocytes which escaped selection in the central lymphoid organs are present in the peripheral repertoire but but are kept under control by multiple diverse peripheral tolerance mechanisms acting either directly on the self-reactive T cell (T-cell intrinsic) or indirectly via additional cells (T-cell extrinsic). Intrinsic mec hanisms include ignorance of autoantigens, anergy, phenotype skewing or activation-induced cell death of autoreactive T lymphocytes, while extrinsic mechanisms act through immature and/ or tolerogenic dendritic cells as well as different types of regulatory cells. Autoimmune diseases are associated with humoral or cell-mediated immune reactions against one or more of the body?s own constituents. Activation and clonal expansion of autoreactive lymhocytes is a crucial step in the pathogenesis of autoimmune diseases. They result from the complex interactions between genetic traits and environmental factors, among which infections are the most likely cause. Several basic mechanisms may be operating whereby an infectious agent actually induces apparent autoimmne reactivity including molecular mimicry, bystander activation, induction of costimulation, polyclonal activation, altered processing and expression of cryptic antigens. Although many questions regarding autotolerance and etiop athogenestis of autoimmunity have yet to be resolved, it is evident that multiple overlapping pathways are operative in establishing, maintaining and breaking autotolerance, as well as during the initiation, progression, and final effector phases of autoimmunity.

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Exploring the Role of Innate Lymphocytes in the Immune System of Bats and Virus-Host Interactions

Viruses ◽

10.3390/v14010150 ◽

2022 ◽

Vol 14 (1) ◽

pp. 150

Author(s):

Wan Rong Sia ◽

Yichao Zheng ◽

Fei Han ◽

Shiwei Chen ◽

Shaohua Ma ◽

...

Keyword(s):

Immune System ◽

Disease Transmission ◽

Viral Infections ◽

Current Knowledge ◽

Future Research ◽

Global Public Health ◽

Immune Systems ◽

Adaptive Immune ◽

Adaptive Immune Cells ◽

Innate Lymphocytes

Bats are reservoirs of a large number of viruses of global public health significance, including the ancestral virus for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the causative agent of coronavirus disease 2019 (COVID-19). Although bats are natural carriers of multiple pathogenic viruses, they rarely display signs of disease. Recent insights suggest that bats have a more balanced host defense and tolerance system to viral infections that may be linked to the evolutionary adaptation to powered flight. Therefore, a deeper understanding of bat immune system may provide intervention strategies to prevent zoonotic disease transmission and to identify new therapeutic targets. Similar to other eutherian mammals, bats have both innate and adaptive immune systems that have evolved to detect and respond to invading pathogens. Bridging these two systems are innate lymphocytes, which are highly abundant within circulation and barrier tissues. These cells share the characteristics of both innate and adaptive immune cells and are poised to mount rapid effector responses. They are ideally suited as the first line of defense against early stages of viral infections. Here, we will focus on the current knowledge of innate lymphocytes in bats, their function, and their potential role in host–pathogen interactions. Moreover, given that studies into bat immune systems are often hindered by a lack of bat-specific research tools, we will discuss strategies that may aid future research in bat immunity, including the potential use of organoid models to delineate the interplay between innate lymphocytes, bat viruses, and host tolerance.

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Physical plasma and leukocytes – immune or reactive?

Biological Chemistry ◽

10.1515/hsz-2018-0224 ◽

2018 ◽

Vol 400 (1) ◽

pp. 63-75 ◽

Cited By ~ 10

Author(s):

Sander Bekeschus ◽

Christian Seebauer ◽

Kristian Wende ◽

Anke Schmidt

Keyword(s):

Wound Healing ◽

Immune System ◽

Plasma Treatment ◽

Immune Cells ◽

The Body ◽

Adaptive Immune ◽

Adaptive Immune Cells ◽

Physical Plasma

AbstractLeukocytes are professionals in recognizing and removing pathogenic or unwanted material. They are present in virtually all tissues, and highly motile to enter or leave specific sites throughout the body. Less than a decade ago, physical plasmas entered the field of medicine to deliver their delicate mix of reactive species and other physical agents for mainly dermatological or oncological therapy. Plasma treatment thus affects leukocytes via direct or indirect means: immune cells are either present in tissues during treatment, or infiltrate or exfiltrate plasma-treated areas. The immune system is crucial for human health and resolution of many types of diseases. It is therefore vital to study the response of leukocytes after plasma treatmentin vitroandin vivo. This review gathers together the major themes in the plasma treatment of innate and adaptive immune cells, and puts these into the context of wound healing and oncology, the two major topics in plasma medicine.

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Roles of Secreted Phospholipases A2 in the Mammalian Immune System

Protein and Peptide Letters ◽

10.2174/0929866521666140819122624 ◽

2014 ◽

Vol 21 (12) ◽

pp. 1201-1208

Author(s):

Igor Krizaj

Keyword(s):

Immune System ◽

Acute Inflammation ◽

The Body ◽

Innate Immune ◽

Future Research ◽

Biological Processes ◽

Phospholipases A2 ◽

Protective Reaction ◽

Severe Pathology ◽

Mammalian Immune System

Secreted phospholipase A2 (sPLA2) molecules constitute a family of proteins that are involved functionally in many biological processes. In particular, they participate in diverse pathophysiological settings as enzymes that release free fatty acids and lysophospholipids from phospholipids in biological membranes, or as ligands for various cellular receptors. In this review the confirmed or expected functions of sPLA2s in the mammalian immune system are surveyed. Some of the twelve mammalian sPLA2 molecules constitute part of the so-called innate immune system by virtue of their antibacterial, antiviral and antifungal activities. They are also involved in acute inflammation, a protective reaction of the body to infection or injury. The acute inflammation sometimes escapes regulation, becomes chronic and can evolve into a severe pathology. One or more types of sPLA2 are involved in asthma, rheumatoid arthritis, sepsis, atherosclerosis, myocardial infarction, Crohn’s disease, ulcerative colitis and cancer. sPLA2s are thus important therapeutic targets as well as biotherapeutic molecules. Improving the selectivity of inhibitors of sPLA2s to be able to target a particular sPLA2 could therefore be one of the most important tasks for future research.

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Introduction to Clinical Immunology: Overview of the Immune Response, Autoimmune Conditions, and Immunosuppressive Therapeutics for Rheumatic Diseases

10.2310/im.1328 ◽

2016 ◽

Author(s):

Steven K. Lundy ◽

Alison Gizinski ◽

David A. Fox

Keyword(s):

Immune Response ◽

Immune System ◽

T Cell ◽

Immune Responses ◽

Autoimmune Diseases ◽

Adaptive Immunity ◽

Cell Populations ◽

Hematopoietic Stem ◽

Innate And Adaptive Immunity ◽

Adaptive Immune

The immune system is a complex network of cells and mediators that must balance the task of protecting the host from invasive threats. From a clinical perspective, many diseases and conditions have an obvious link to improper functioning of the immune system, and insufficient immune responses can lead to uncontrolled acute and chronic infections. The immune system may also be important in tumor surveillance and control, cardiovascular disease, health complications related to obesity, neuromuscular diseases, depression, and dementia. Thus, a working knowledge of the role of immunity in disease processes is becoming increasingly important in almost all aspects of clinical practice. This review provides an overview of the immune response and discusses immune cell populations and major branches of immunity, compartmentalization and specialized immune niches, antigen recognition in innate and adaptive immunity, immune tolerance toward self antigens, inflammation and innate immune responses, adaptive immune responses and helper T (Th) cell subsets, components of the immune response that are important targets of treatment in autoimmune diseases, mechanisms of action of biologics used to treat autoimmune diseases and their approved uses, and mechanisms of other drugs commonly used in the treatment of autoimmune diseases. Figures show the development of erythrocytes, platelets, lymphocytes, and other immune system cells originating from hematopoietic stem cells that first reside in the fetal liver and later migrate to the bone marrow, antigen–major histocompatibility complex recognition by T cell receptor control of T cell survival and activation, and Th cells as central determinants of the adaptive immune response toward different stimuli. Tables list cell populations involved in innate and adaptive immunity, pattern recognition receptors with known ligands, autoantibody-mediated human diseases: examples of pathogenic mechanisms, selected Food and Drug Administration–approved autoimmune disease indications for biologics, and mechanism of action of biologics used to treat autoimmune diseases. This review contains 3 highly rendered figures, 5 tables, and 64 references.

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Fluoride Exposure Induces Inhibition of Sodium-and Potassium-Activated Adenosine Triphosphatase (Na+, K+-ATPase) Enzyme Activity: Molecular Mechanisms and Implications for Public Health

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph16081427 ◽

2019 ◽

Vol 16 (8) ◽

pp. 1427 ◽

Cited By ~ 13

Author(s):

Declan Timothy Waugh

Keyword(s):

Enzyme Activity ◽

Atpase Activity ◽

Molecular Mechanisms ◽

Chemical Elements ◽

Biological Pathways ◽

Normal Brain ◽

Biological Interface ◽

Increased Risk ◽

And Function ◽

Risk Of Cancer

In this study, several lines of evidence are provided to show that Na + , K + -ATPase activity exerts vital roles in normal brain development and function and that loss of enzyme activity is implicated in neurodevelopmental, neuropsychiatric and neurodegenerative disorders, as well as increased risk of cancer, metabolic, pulmonary and cardiovascular disease. Evidence is presented to show that fluoride (F) inhibits Na + , K + -ATPase activity by altering biological pathways through modifying the expression of genes and the activity of glycolytic enzymes, metalloenzymes, hormones, proteins, neuropeptides and cytokines, as well as biological interface interactions that rely on the bioavailability of chemical elements magnesium and manganese to modulate ATP and Na + , K + -ATPase enzyme activity. Taken together, the findings of this study provide unprecedented insights into the molecular mechanisms and biological pathways by which F inhibits Na + , K + -ATPase activity and contributes to the etiology and pathophysiology of diseases associated with impairment of this essential enzyme. Moreover, the findings of this study further suggest that there are windows of susceptibility over the life course where chronic F exposure in pregnancy and early infancy may impair Na + , K + -ATPase activity with both short- and long-term implications for disease and inequalities in health. These findings would warrant considerable attention and potential intervention, not to mention additional research on the potential effects of F intake in contributing to chronic disease.

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Primer immunhiány és autoimmun betegségek

Orvosi Hetilap ◽

10.1556/650.2018.31064 ◽

2018 ◽

Vol 159 (23) ◽

pp. 908-918

Author(s):

Györgyi Műzes ◽

Ferenc Sipos

Keyword(s):

Immune System ◽

Autoimmune Diseases ◽

Primary Immunodeficiency ◽

Adaptive Immune System ◽

Infectious Complications ◽

Primary Immunodeficiencies ◽

Cellular Mechanisms ◽

Adaptive Immune ◽

Solid Malignancies ◽

Autoimmune Phenomena

Abstract: Primary immunodeficiencies consist of a group of genetically heterogeneous immune disorders affecting distinct elements of the innate and adaptive immune system. Patients with primary immunodeficiency are more prone to develop not only recurrent infections, but non-infectious complications, like inflammatory or granulomatous conditions, lymphoproliferative and solid malignancies, autoinflammatory disorders, and a broad spectrum of autoimmune diseases. The concomitant appearance of primary immunodeficiency and autoimmunity appears to be rather paradoxical, therefore making the diagnosis of immunodeficiency patients with autoimmune complications challenging. Mutations of one or more genes playing a fundamental role in immunoregulation and/or immune tolerance network are thought to be responsible for primary immunodeficiencies. The diverse immunological abnomalities along with the compensatory and excessive sustained inflammatory response result in tissue damage and finally in manifestation of organ-, cell-specific or systemic autoimmune diseases. Several forms of primary immunodeficiency disorders are characterized by a variety of specific autoimmune phenomena. This overview addresses the spectrum of autoimmune diseases associated with primary immunodeficiencies, and explores the molecular and cellular mechanisms underlying abnormalities of the immune system. The case presented finally highlights that both the recognition of autoimmune diseases in association with immunodeficiencies and the diagnosis of immunodefiency in those phenotypes with predominant autoimmunity could be challenging. Orv Hetil. 2018; 159(23): 908–918.

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