Immune Response in Thyroid Cancer: Widening the Boundaries

The association between thyroid cancer and thyroid inflammation has been repeatedly reported and highly debated in the literature. In fact, both molecular and epidemiological data suggest that these diseases are closely related and this association reinforces that the immune system is important for thyroid cancer progression. Innate immunity is the first line of defensive response. Unlike innate immune responses, adaptive responses are highly specific to the particular antigen that induced them. Both branches of the immune system may interact in antitumor immune response. Major effector cells of the immune system that directly target thyroid cancer cells include dendritic cells, macrophages, polymorphonuclear leukocytes, mast cells, and lymphocytes. A mixture of immune cells may infiltrate thyroid cancer microenvironment and the balance of protumor and antitumor activity of these cells may be associated with prognosis. Herein, we describe some evidences that immune response may be important for thyroid cancer progression and may help us identify more aggressive tumors, sparing the vast majority of patients from costly unnecessary invasive procedures. The future trend in thyroid cancer is an individualized therapy.

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Role of MicroRNAs in Obesity-Induced Metabolic Disorder and Immune Response

Journal of Immunology Research ◽

10.1155/2018/2835761 ◽

2018 ◽

Vol 2018 ◽

pp. 1-8 ◽

Cited By ~ 10

Author(s):

Hong Zhong ◽

Minjuan Ma ◽

Tingming Liang ◽

Li Guo

Keyword(s):

Immune Response ◽

Immune System ◽

Metabolic Disorder ◽

Metabolic Regulation ◽

Public Health Issue ◽

Metabolic Dysfunction ◽

Global Public Health ◽

Adaptive Responses ◽

Living Organisms

In all living organisms, metabolic homeostasis and the immune system are the most fundamental requirements for survival. Recently, obesity has become a global public health issue, which is the cardinal risk factor for metabolic disorder. Many diseases emanating from obesity-induced metabolic dysfunction are responsible for the activated immune system, including innate and adaptive responses. Of note, inflammation is the manifest accountant signal. Deeply studied microRNAs (miRNAs) have participated in many pathways involved in metabolism and immune responses to protect cells from multiple harmful stimulants, and they play an important role in determining the progress through targeting different inflammatory pathways. Thus, immune response and metabolic regulation are highly integrated with miRNAs. Collectively, miRNAs are the new targets for therapy in immune dysfunction.

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Cellular side of acquired immunity (T cells)

10.1093/med/9780199642489.003.0049 ◽

2013 ◽

Cited By ~ 1

Author(s):

Assia Eljaafari ◽

Pierre Miossec

Keyword(s):

Immune Response ◽

T Cells ◽

Immune System ◽

Disease Process ◽

T Cell Response ◽

Th2 Cells ◽

Cell Mediated Immunity ◽

Immune Effector ◽

Effector Cells ◽

Th22 Cells

The adaptive T-cell response represents the most sophisticated component of the immune response. Foreign invaders are recognized first by cells of the innate immune system. This leads to a rapid and non-specific inflammatory response, followed by induction of the adaptive and specific immune response. Different adaptive responses can be promoted, depending on the predominant effector cells that are involved, which themselves depend on the microbial/antigen stimuli. As examples, Th1 cells contribute to cell-mediated immunity against intracellular pathogens, Th2 cells protect against parasites, and Th17 cells act against extracellular bacteria and fungi that are not cleared by Th1 and Th2 cells. Among the new subsets, Th22 cells protect against disruption of epithelial layers secondary to invading pathogens. Finally these effector subsets are regulated by regulatory T cells. These T helper subsets counteract each other to maintain the homeostasis of the immune system, but this balance can be easily disrupted, leading to chronic inflammation or autoimmune diseases. The challenge is to detect early changes in this balance, prior to its clinical expression. New molecular tools such as microarrays could be used to determine the predominant profile of the immune effector cells involved in a disease process. Such understanding should provide better therapeutic tools to counteract deregulated effector cells.

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RAGE and TLRs as Key Targets for Antiatherosclerotic Therapy

BioMed Research International ◽

10.1155/2018/7675286 ◽

2018 ◽

Vol 2018 ◽

pp. 1-10 ◽

Cited By ~ 4

Author(s):

Wioletta Olejarz ◽

Dominika Łacheta ◽

Alicja Głuszko ◽

Ewa Migacz ◽

Wojciech Kukwa ◽

...

Keyword(s):

Immune System ◽

Inflammatory Responses ◽

Adaptive Immune System ◽

Primary Response ◽

Type I ◽

Adaptive Responses ◽

Effector Cells ◽

Antiatherosclerotic Therapy ◽

Molecular Patterns ◽

Direct Killing

Receptor for advanced glycation end-products (RAGE) and toll-like receptors (TLRs) are the key factors indicating a danger to the organism. They recognize the microbial origin pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs). The primary response induced by PAMPs or DAMPs is inflammation. Excessive stimulation of the innate immune system occurs in arterial wall with the participation of effector cells. Persistent adaptive responses can also cause tissue damage and disease. However, inflammation mediated by the molecules innate responses is an important way in which the adaptive immune system protects us from infection. The specific detection of PAMPs and DAMPs by host receptors drives a cascade of signaling that converges at nuclear factor-κB (NF-κB) and interferon regulatory factors (IRFs) and induces the secretion of proinflammatory cytokines, type I interferon (IFN), and chemokines, which promote direct killing of the pathogen. Therefore, signaling of these receptors’ pathways also appear to present new avenue for the modulation of inflammatory responses and to serve as potential novel therapeutic targets for antiatherosclerotic therapy.

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A qualitative mathematical model of immunocompetence with applications to SARS-CoV-2 immunity

10.1101/2021.12.08.471857 ◽

2021 ◽

Author(s):

Javier Burgos-Salcedo

Keyword(s):

Mathematical Model ◽

Immune Response ◽

Immune System ◽

Random Graphs ◽

Practical Method ◽

Higher Order ◽

Effector Cells ◽

Emergent Structure

A qualitative mathematical model of the notion of immunocompetence is developed, based on the formalism of Memory Evolutive Systems (MES), from which, immunocompetence is defined as an emergent structure of a higher order arising from the signal networks that are established between effector cells and molecules of the immune response in the presence of a given antigen. In addition, a possible mechanism of functorial nature is proposed, which may explain how immunocompetence is achieved in an organism endowed with innate and adaptive components of its immune system. Finally, a practical method to measure the immunocompetence status is established, using elements of the theory of small random graphs and taking into account the characteristics of the immune networks, established through transcriptional studies, of patients with severe COVID-19 and healthy patients, assuming that both types of patients were vaccinated with an effective biological against SARS-CoV-2.

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Molecular half-full mechanisms by phagocityc cells on invasive Aspergilosis

Colombia Medica ◽

10.25100/cm.v43i1.1064 ◽

2012 ◽

pp. 95-102

Author(s):

Karla Rossanet Dzul-Rosado ◽

Viridiana Martínez-Campos ◽

Gaspar Peniche-Lara ◽

Jorge E Zavala-Castro

Keyword(s):

Immune System ◽

Host Immune System ◽

Adaptive Responses ◽

Phagocytic Cells ◽

Effector Cells ◽

Surface Receptors ◽

Molecular Receptors ◽

Tnf Α ◽

Particle Recognition ◽

Ifn Γ

Fungus from the Aspergillus genus mainly affects lung tissue, occurring when the integrity of the host immune system is compromised. The human body uses immunocompetence conditions from mechanical and enzymatic defenses and the action of the innate immune system cells and also uses adaptive responses to control infection. Neutrophils, macrophages, and dendritic cells are critical as antifungal effector cells possess surface receptors that recognize fungal structures and trigger specific responses. TLRs and Dectin-1 the most studied for this interaction. TLRs are responsible for the production and release of cytokines and Dectin-1 is essential in the phagocytosis of the particle recognition and production of ROS. The best-studied cytokines and its crucial role in the response to Aspergillus spp. are TNF-α, IFN-γ, and IL-12. In this work, we reviewed the main mechanisms related to molecular receptors on phagocytic cells involved in the recognition of Aspergillus spp. Understanding the immune response in situations of immunocompetence and its comparison in immunodeficient organisms could provide alternatives to control invasive aspergillosis.

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Therapeutic Approaches for COVID-19 Based on the Dynamics of Interferon-mediated Immune Responses

10.20944/preprints202003.0206.v2 ◽

2020 ◽

Cited By ~ 5

Author(s):

Farbod Shahabi nezhad ◽

Pouria Mosaddeghi ◽

Manica Negahdaripour ◽

Zahra Dehghani ◽

Mitra Farahmandnejad ◽

...

Keyword(s):

Immune Response ◽

Immune System ◽

Immune Responses ◽

Synergistic Effects ◽

The Elderly ◽

Innate Immune ◽

Response Threshold ◽

Innate Immune Responses ◽

Optimum Approach ◽

Novel Virus

As the outbreak of COVID-19 has accelerated, an urgent need for finding strategies to combat the virus is growing. Thus, gaining more knowledge on the pathogenicity mechanisms of SARS-CoV-2, the causing agent of COVID-19, and its interaction with the immune system is of utmost importance. Although this novel virus is not well known yet, its structural and genetic similarity with SARS-CoV as well as the comparable pattern of age-mortality relations suggest that the previous findings on SARS can be applicable for COVID-19. Therefore, a systems biology study was conducted to investigate the most important signaling pathways activated by the virus. The results were then validated through a literature review on COVID-19 and the other closely related viruses, SARS and MERS. Interferons have shown to play a crucial role in the defense against coronavirus diseases. CoV can impede the interferon induction in humans. Moreover, STAT1, a key protein in the interferon-mediated immune response, is antagonized by the virus. This could explain the increased response threshold of immune cells to IFNs during CoV infections. A vivid correlation between the innate immune response threshold and the fatality rates in COVID-19 can be found. Differences in the dynamics of the interferon-related innate immune responses in children, adults, and elderly may explain the reported fatality rates. The increased mortality rates in the elderly can be explained by the higher threshold of interferon-mediated immune responses. Earlier induction of interferons in children and their less developed immune system could contribute to their near to zero fatality rate. Administration of interferon-inducing agents, such as poly (ICLC), could reduce the mortality of SARS at the very early stages of the disease. Interferon-γ combination with an interferon-I might induce synergistic effects and maximize the benefits. However, in-depth research is needed to validate it and determine the optimum dosage and timing to prevent unwanted results. Such interventions can act as a double-edged sword and aid the imbalance of the immune reactions, which may occur at the later stages of the disease. With the advancement of the disease and the virus overload, the responses would shift toward immnopathogenic over-reactions and probably cytokine storm. Moderating the activity of the immune system and supportive care in such conditions might be the optimum approach.

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Indoleamine-2,3-Dioxygenase in Thyroid Cancer Cells Suppresses Natural Killer Cell Function by Inhibiting NKG2D and NKp46 Expression via STAT Signaling Pathways

Journal of Clinical Medicine ◽

10.3390/jcm8060842 ◽

2019 ◽

Vol 8 (6) ◽

pp. 842 ◽

Cited By ~ 3

Author(s):

Arum Park ◽

Yunjeong Yang ◽

Yunhee Lee ◽

Mi Sun Kim ◽

Young-Jun Park ◽

...

Keyword(s):

Thyroid Cancer ◽

Immune System ◽

Nk Cells ◽

Cancer Cells ◽

Natural Killer ◽

Cell Function ◽

Nk Cell ◽

Receptor Expression ◽

Indoleamine 2,3 Dioxygenase ◽

Thyroid Cancer Cells

Natural killer (NK) cells are key players in the immune system. They use receptors on their cell surface to identify target cells. However, to escape being killed by the immune system, cancer cells such as thyroid cancer cells, use various methods to suppress the function of NK cells. Thus, this study aims to elucidate how thyroid cancer cells downregulate NK cell function in a co-culture system. We found that thyroid cancer cells suppress NK cell cytotoxicity and inhibit the expression of activating receptors, such as NKG2D and NKp46, by regulating indoleamine 2,3-dioxygenase (IDO). Also, thyroid cancer cells produce kynurenine using IDO, which causes NK cell dysfunction. Kynurenine enters NK cells via the aryl hydrocarbon receptor (AhR) on the surfaces of the NK cells, which decreases NK cell function and NK receptor expression via the signal transducer and activator of transcription (STAT) 1 and STAT3 pathways. In addition, STAT1 and STAT3 directly regulated the expression of NKG2D and NKp46 receptors by binding to the promoter region. Conclusively, NK cell function may be impaired in thyroid cancer patients by IDO-induced kynurenine production. This implies that IDO can be used as a target for thyroid cancer therapeutics aiming at improving NK cell function.

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CRSP8 promotes thyroid cancer progression by antagonizing IKKα-induced cell differentiation

Cell Death and Differentiation ◽

10.1038/s41418-020-00656-0 ◽

2020 ◽

Author(s):

Yina Liao ◽

Yijun Hua ◽

Yizhuo Li ◽

Changlin Zhang ◽

Wendan Yu ◽

...

Keyword(s):

Thyroid Cancer ◽

Cell Growth ◽

Cancer Cells ◽

Cancer Progression ◽

Direct Interaction ◽

Anaplastic Thyroid Cancer ◽

Human Thyroid ◽

Induced Apoptosis ◽

Thyroid Cancer Cells

Abstract CRSP8 plays an important role in recruiting mediators to genes through direct interaction with various DNA-bound transactivators. In this study, we uncovered the unique function of CRSP8 in suppressing thyroid cancer differentiation and promoting thyroid cancer progression via targeting IKKα signaling. CRSP8 was highly expressed in human thyroid cancer cells and tissues, especially in anaplastic thyroid cancer (ATC). Knockdown of CRSP8 suppressed cell growth, migration, invasion, stemness, and induced apoptosis and differentiation in ATC cells, while its overexpression displayed opposite effects in differentiated thyroid cancer (DTC) cells. Mechanistically, CRSP8 downregulated IKKα expression by binding to the IKKα promoter region (−257 to −143) to negatively regulate its transcription. Knockdown or overexpression of IKKα significantly reversed the expression changes of the differentiation and EMT-related markers and cell growth changes mediated by CRSP8 knockdown or overexpression in ATC or DTC cells. The in vivo study also validated that CRSP8 knockdown inhibited the growth of thyroid cancer by upregulating IKKα signaling in a mouse model of human ATC. Furthermore, we found that CRSP8 regulated the sensitivity of thyroid cancer cells to chemotherapeutics, including cisplatin and epirubicin. Collectively, our results demonstrated that CRSP8 functioned as a modulator of IKKα signaling and a suppressor of thyroid cancer differentiation, suggesting a potential therapeutic strategy for ATC by targeting CRSP8/IKKα pathway.

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CHARACTERISTICS OF CELLULAR COMPARTMENT CHANGES OF IMMUNE SYSTEM IN THE PATIENTS WITH CHRONIC POLYPOUS RHINOSINUSITIS DEPEND ON EFFICIENCY OF DRUG THERAPY

Medical Immunology (Russia) ◽

10.15789/1563-0625-2019-4-715-724 ◽

2019 ◽

Vol 21 (4) ◽

pp. 715-724

Author(s):

E. L. Savlevich ◽

A. V. Zurochka ◽

S. V. Khaidukov

Keyword(s):

Immune Response ◽

Immune System ◽

Drug Therapy ◽

T Lymphocytes ◽

Cytotoxic T Lymphocytes ◽

Nasal Polyps ◽

Inflammatory Process ◽

Nkt Cells ◽

Absolute Number ◽

Effector Cells

Despite numerous attempts to control the course of chronic rhinosinusitis with nasal polyps (CRSwNP) by means of pharmacological treatment and new surgical approaches, the majority of patients experience lifelong persistence of this disorder, at recurrence rates of 50-60% within 18 months after surgical treatment. Since CRSwNP is a chronic persistent inflammatory process, it affects the entire body condition, including the state of systemic immune response. An elevation of NK (CD3-CD16+CD56+), activated NK (CD8+CD3-), NKT cells (CD16+CD56+CD3+), Treg (CD4+CD25brightCD127low to neg) cells and activated T-lymphocytes (CD3+CD25+) was revealed elsewhere among all the patients with CRSwNP, using a flow ytometry method. There was no difference between various disease phenotypes. We analyzed the status of cellular component of systemic immunity, dependent on clinical course of the disease and efficiency of the administered therapy of CRSwNP. The patients were divided into three subgroups. The follow-up period was 1 year. The first group comprised the patients who showed positive dynamics after conservative therapy, resulting into regression of nasal polyps and their grade than a year ago. The second group included the patients in whom the size of polyps remained the same. The third group included the patients with higher incidence of nasal polyps than a year ago.We have shown a decrease of Treg, NKT cells, NK and activated NK, cytotoxic T-lymphocytes (CD3+CD8+), activated T-cell numbers in clinical group 3 with aggressive growth of polyps and low effect of standard therapy, which may cause deterioration of the immune system cellular populations, accompanied by presence of persistent productive inflammatory process of nasal cavity and paranasal sinuses. In the second group, a significant elevation of total lymphocyte number, total and activated T cells, T helpers (CD3+CD4+), cytotoxic T lymphocytes, NK and NKT cells was shown. Meanwhile, a decrease in absolute number of activated NK was observed despite the NK growth. Therefore, we can assume that the mechanism of their activation was disturbed and compensated by production of NKT cells and cytotoxic T lymphocytes. Moreover, we have shown in this group that the absolute number of Treg cells is increased; and these cells had a suppressive influence on effector cells of adaptive immune response, thus inducing incomplete elimination of infectious agents, which contribute to permanent incomplete course of inflammatory process. Chronic inflammatory process in CRSwNP affects systemic cellular immunity depending on the morbidity characteristics in the course of pathological process. The maximal intensity of systemic cellular immunity is observed in the group of patients that require permanent basic drug therapy. In case of aggressive CRSwNP and failure of standard drug therapy, we observed a decrease in absolute numbers of effector cells, along with decreased Treg lymphocyte numbers which may explain inefficient immune regulation of inflammatory process and medical interventions in this group of patients.

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p53 Activation Effect in the Balance of T Regulatory and Effector Cell Subsets in Patients With Thyroid Cancer and Autoimmunity

Frontiers in Immunology ◽

10.3389/fimmu.2021.728381 ◽

2021 ◽

Vol 12 ◽

Author(s):

Andrea Arena ◽

Antonio Stigliano ◽

Eugenia Belcastro ◽

Ezio Giorda ◽

Maria Manuela Rosado ◽

...

Keyword(s):

Immune Response ◽

Cell Death ◽

Thyroid Cancer ◽

Programmed Cell Death ◽

Cancer Patients ◽

Solid Cancer ◽

Host Immune System ◽

Effector Cells ◽

T Effector Cells ◽

P53 Activation

Carcinomas evade the host immune system by negatively modulating CD4+ and CD8+ T effector lymphocytes through forkhead box protein 3 (FOXP3) positive T regulatory cells’ increased activity. Furthermore, interaction of the programmed cell death 1 (PD1) molecule and its ligand programmed cell death ligand 1 (PDL1) inhibits the antitumor activity of PD1+ T lymphocytes. Immunotherapy has become a powerful strategy for tailored cancer patients’ treatment both in adult and pediatric patients aiming to generate potent antitumor responses. Nevertheless, immunotherapies can generate autoimmune responses. This study aimed to investigate the potential effect of the transformation-related protein 53 (p53) reactivation by a peptide-based inhibitor of the MDM2/MDM4 heterodimer (Pep3) on the immune response in a solid cancer, i.e., thyroid carcinoma frequently presenting with thyroid autoimmunity. In peripheral blood mononuclear cell of thyroid cancer patients, Pep3 treatment alters percentages of CD8+ and CD4+ T regulatory and CD8+ and CD4+ T effector cells and favors an anticancer immune response. Of note that reduced frequencies of activated CD8+ and CD4+ T effector cells do not support autoimmunity progression. In evaluating PD1 expression under p53 activation, a significant decrease of activated CD4+PD1+ cells was detected in thyroid cancer patients, suggesting a defective regulation in the initial activation stage, therefore generating a protective condition toward autoimmune progression.

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