Interferons: role in cancer therapy

Immunotherapy ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 833-855 ◽  
Author(s):  
Mohadeseh Haji Abdolvahab ◽  
Behrad Darvishi ◽  
Mohammad Zarei ◽  
Keivan Majidzadeh-A ◽  
Leila Farahmand
Keyword(s):  
Immune System ◽  
Cancer Therapy ◽  
Immune Cells ◽  
Biological Function ◽  
Host Cells ◽  
Combination Therapies ◽  
Chronic Stimulation ◽  
Induce Resistance ◽  
Extreme Responses ◽  
Stimulation Of

Interferons (IFNs) are a group of signaling cytokines, secreted by host cells to induce protection against various disorders. IFNs can directly impact on tumor cells or indirectly induce the immune system to protect host cells. The expression levels of IFNs and its functions of are excellently modulated in a way to protect host cells from probable toxicities caused by extreme responses. The efficacy of anticancer therapies is correlated to IFNs signaling. Although IFN signaling is involved in induction of antitumor responses, chronic stimulation of the IFN signaling pathway can induce resistance to various antineoplasm therapies. Hence, IFNs are expressed by both cancer and immune cells, and modulate their biological function. Understanding this mechanism of action might be a key target of combination therapies.

scholarly journals Search for receptors in immune cells that bind cancer cell antigens and their activation in silent cases

2019 ◽  
Author(s):  
Wenfa Ng
Keyword(s):  
Immune System ◽  
Amino Acid ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Immune Cells ◽  
Immune Cell ◽  
Checkpoint Inhibitors ◽  
Host Cells ◽  
Immune Receptor

The immune checkpoint plays an important role in keeping immune cells in check for protecting tissues and organs from attack by the body’s own immune system. Similar concepts also apply in how cancer cells managed to fool immune cells through the surface display of particular antigens that mimic those exhibited by normal body cells. Specifically, cancer cells display antigens that bind to receptors on immune cells that subsequently prevent an attack on the cancer cells. Such binding between cancer antigens and immune cell receptors can be prevented through the use of checkpoint inhibitors antibodies specific for particular receptors on immune cells; thereby, unleashing immune cells to mount an immune response against cancer cells. While demonstrating good remissions in many patients where tumours shrunk substantially after administration of checkpoint inhibitors, cases exist where an overactivated immune system cause harm to organs and tissues culminating in multiple organ failure. Analysis of such toxicity effects of checkpoint inhibitors revealed that generic nature of targeted immune receptor plays a pivotal role in determining extent of side effects. Specifically, if the target immune receptor participates in checkpoints that prevent immune cells from attacking host cells, unleashing such receptors in cancer therapy may have untoward effects on patient’s health. Hence, the goal should be the selection of immune cell receptor specific to cancer cell antigens and which does not bind antigens or ligands displayed by the body’s cells. Such receptors would provide ideal targets for the development of checkpoint inhibitor antibodies for unleashing immune cells against cancer cells. To search for non-generic receptors that bind cancer cell antigens only, a combined computational and experimental approach could be used where ensemble of surface antigens on cancer cells and available receptors on immune cells could be profiled by biochemical assays. Downstream purification of ligands and receptors would provide for both structural elucidation and amino acid sequencing useful for bioinformatic search of homologous sequences. Knowledge of the antigens’ and receptors’ structures and amino acid sequence would subsequently serve as inputs to computational algorithms that models molecular docking events between receptor and antigen. This paves the way for heterologous expression of putative ligand and receptor in cell lines cultured in co-culture format for assessing binding between ligand and receptor, and more importantly, its physiological effects. Ability of immune receptor to bind to ligands on normal cells could also be assessed. Similar co-culture studies could be conducted with cancer cells and different immune cell types to check for reproducibility of observed effect in cell lines. Finally, antibodies could be raised for candidate receptors whose inhibition would not result in systemic attack of immune cells on host cells.

scholarly journals Extracellular Vesicles Released by Leishmania: Impact on Disease Development and Immune System Cells

2021 ◽  
Author(s):  
Rogéria Cristina Zauli ◽  
Andrey Sladkevicius Vidal ◽  
Talita Vieira Dupin ◽  
Aline Correia Costa de Morais ◽  
Wagner Luiz Batista ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Extracellular Vesicles ◽  
Virulence Factors ◽  
Immune Cells ◽  
Diagnostic Tool ◽  
Experimental Models ◽  
Host Cells ◽  
Disease Development ◽  
Leishmania Spp

Leishmania spp. release extracellular vesicles (EVs) containing parasite molecules, including several antigens and virulence factors. These EVs can interact with the host cells, such as immune cells, contributing to the parasite–host relationship. Studies have demonstrated that Leishmania-EVs can promote infection in experimental models and modulate the immune response. Although the immunomodulatory effect has been demonstrated, Leishmania-EVs can deliver parasite antigens and therefore have the potential for use as a new diagnostic tool and development of new therapeutic and vaccine approaches. This review aims to bring significant advances in the field of extracellular vesicles and Leishmania, focusing on their role in the cells of the immune system.

scholarly journals Search for receptors in immune cells that bind cancer cell antigens and their activation in silent cases

2019 ◽  
Author(s):  
Wenfa Ng
Keyword(s):  
Immune System ◽  
Amino Acid ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Immune Cells ◽  
Immune Cell ◽  
Checkpoint Inhibitors ◽  
Host Cells ◽  
Immune Receptor

The immune checkpoint plays an important role in keeping immune cells in check for protecting tissues and organs from attack by the body’s own immune system. Similar concepts also apply in how cancer cells managed to fool immune cells through the surface display of particular antigens that mimic those exhibited by normal body cells. Specifically, cancer cells display antigens that bind to receptors on immune cells that subsequently prevent an attack on the cancer cells. Such binding between cancer antigens and immune cell receptors can be prevented through the use of checkpoint inhibitors antibodies specific for particular receptors on immune cells; thereby, unleashing immune cells to mount an immune response against cancer cells. While demonstrating good remissions in many patients where tumours shrunk substantially after administration of checkpoint inhibitors, cases exist where an overactivated immune system cause harm to organs and tissues culminating in multiple organ failure. Analysis of such toxicity effects of checkpoint inhibitors revealed that generic nature of targeted immune receptor plays a pivotal role in determining extent of side effects. Specifically, if the target immune receptor participates in checkpoints that prevent immune cells from attacking host cells, unleashing such receptors in cancer therapy may have untoward effects on patient’s health. Hence, the goal should be the selection of immune cell receptor specific to cancer cell antigens and which does not bind antigens or ligands displayed by the body’s cells. Such receptors would provide ideal targets for the development of checkpoint inhibitor antibodies for unleashing immune cells against cancer cells. To search for non-generic receptors that bind cancer cell antigens only, a combined computational and experimental approach could be used where ensemble of surface antigens on cancer cells and available receptors on immune cells could be profiled by biochemical assays. Downstream purification of ligands and receptors would provide for both structural elucidation and amino acid sequencing useful for bioinformatic search of homologous sequences. Knowledge of the antigens’ and receptors’ structures and amino acid sequence would subsequently serve as inputs to computational algorithms that models molecular docking events between receptor and antigen. This paves the way for heterologous expression of putative ligand and receptor in cell lines cultured in co-culture format for assessing binding between ligand and receptor, and more importantly, its physiological effects. Ability of immune receptor to bind to ligands on normal cells could also be assessed. Similar co-culture studies could be conducted with cancer cells and different immune cell types to check for reproducibility of observed effect in cell lines. Finally, antibodies could be raised for candidate receptors whose inhibition would not result in systemic attack of immune cells on host cells.

scholarly journals Immune System Evasion Mechanisms in Staphylococcus aureus: Current Understanding

2020 ◽  
Vol 14 (4) ◽  
pp. 2219-2234
Author(s):  
Hesham A. Malak ◽  
Hussein H. Abulreesh ◽  
Sameer R. Organji ◽  
Khaled Elbanna ◽  
Mohammed R. Shaaban ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Immune System ◽  
Soft Tissue ◽  
Immune Cells ◽  
Bloodstream Infections ◽  
Host Cells ◽  
Human Pathogen ◽  
Immune Systems ◽  
Wide Range ◽  
New Strategy

Staphylococcus aureus is a major human pathogen that may cause a wide range of infections and is a frequent cause of soft tissue and bloodstream infections. It is a successful pathogen due to its collective virulence factors and its ability to evade the host immune systems. The review aims to highlight how S. aureus destroys and damage the host cells and explains how immune cells can respond to this pathogen. This review may also provide new insights that may be useful for developing new strategy for combating MRSA and its emerging clones such as community-associated methicillin-resistant S. aureus (CA-MRSA).

scholarly journals Pathogenesis of Bone Alterations in Gaucher Disease: The Role of Immune System

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Juan Marcos Mucci ◽  
Paula Rozenfeld
Keyword(s):  
Immune System ◽  
Gaucher Disease ◽  
Autosomal Recessive ◽  
Bone Pathology ◽  
Chronic Stimulation ◽  
Osteolytic Lesions ◽  
Lysosomal Disorder ◽  
Skeletal Bone ◽  
Stimulation Of

Gaucher, the most prevalent lysosomal disorder, is an autosomal recessive inherited disorder due to a deficiency of glucocerebrosidase. Glucocerebrosidase deficiency leads to the accumulation of glucosylceramide primarily in cells of mononuclear-macrophage lineage. Clinical alterations are visceral, hematological, and skeletal. Bone disorder in Gaucher disease produces defects on bone metabolism and structure and patients suffer from bone pain and crisis. Skeletal problems include osteopenia, osteoporosis, osteolytic lesions, and osteonecrosis. On the other hand a chronic stimulation of the immune system is a well-accepted hallmark in this disease. In this review we summarize the latest findings in the mechanisms leading to the bone pathology in Gaucher disease in relationship with the proinflammatory state.

scholarly journals Emerging Dynamics of Macrophage Cellular Senescence and Immunosenescence in Governing Organismal Aging and Disease: Concepts and Opportunities

2021 ◽  
Author(s):  
Rohit Sharma
Keyword(s):  
Immune System ◽  
Cellular Senescence ◽  
Immune Cells ◽  
Innate Immune ◽  
Host Cells ◽  
Macrophage Phenotype ◽  
Immune Functions ◽  
Biological Impact ◽  
Age Related ◽  
Disease Concepts

An intricate relationship between impaired immune functions and the age-related accumulation of tissue senescent cells (SC) is rapidly emerging. The immune system is unique as it undergoes mutually inclusive and deleterious processes of immunosenescence and cellular senescence with advancing age. While factors inducing immunosenescence and cellular senescence may be shared, however, both these processes are fundamentally different which holistically influence the aging immune system. Immunosenescence is a well-characterized phenomenon, but our understanding and biological impact of cellular senescence in immune cells, especially in the innate immune cells such as macrophages, is only beginning to be understood. Tissue-resident macrophages are long-lived, and while functioning in tissue-specific and niche-specific microenvironments, senescence in macrophages can be directly influenced by senescent host cells which may impact organismal aging. In addition, evidence of age-associated immunometabolic changes as drivers of altered macrophage phenotype and functions such as inflamm-aging is also emerging. The present review describes the emerging impact of cellular senescence vis-à-vis immunosenescence in aging macrophages, its biological relevance with other senescent non-immune cells, and known immunometabolic regulators. Gaps in our present knowledge, as well as strategies aimed at understanding cellular senescence and its therapeutics in the context of macrophages, have been reviewed.

Triggering of Toll-like Receptors in Old Individuals. Relevance for Vaccination

2019 ◽  
Vol 25 (39) ◽  
pp. 4163-4167 ◽  
Author(s):  
Nahid Zareian ◽  
Stefano Aprile ◽  
Laura Cristaldi ◽  
Mattia Emanuela Ligotti ◽  
Sonya Vasto ◽  
...  
Keyword(s):  
Immune System ◽  
Immune Cells ◽  
Vaccine Efficacy ◽  
Successful Aging ◽  
Toll Like Receptors ◽  
Tlr Agonists ◽  
Synergistic Activation ◽  
General Decline ◽  
Stimulation Of

Aging is characterized by a general decline in a range of physiological functions, with a consequent increase in the risk of developing a variety of chronic diseases and geriatric syndromes. Additionally, increasing age is accompanied by a progressive decline in both innate and acquired immune system, referred to as immunosenescence. This impaired ability to mount an efficient immune response after exposure to microorganisms or vaccines represents a major challenge in acquiring protection against pathogens in aging. Therefore, there is still a great need for vaccines that are tailored to optimally stimulate the aged immune system, thus promoting more successful aging. Various strategies can be used to improve vaccine efficacy in old people. Despite this, metaanalyses have clearly shown that the magnitude of protection obtained remains lower in older adults. Recent studies show that stimulation of Toll-like receptors, using stimulatory ligands, can enhance vaccine efficacy by a number of mechanisms, including the activation of innate immune cells and the consequent production of inflammatory cytokines. Therefore, a possible strategy for more effective vaccination in the older population is the triggering of multiple TLRs, using a combined adjuvant for the synergistic activation of cellular immunity. Preliminary in vitro data suggest that in humans the presence of multiple TLR agonists can result in the greater stimulation of antigen-specific immune responses in immune cells both in the young healthy and in the immune senescent older donors. These data suggest that appropriately selected combinations of TLR agonists could enhance the efficacy of vaccination mediated immunity in older people.

scholarly journals Listeria monocytogenes Desensitizes Immune Cells to Subsequent Ca2+ Signaling via Listeriolysin O-Induced Depletion of Intracellular Ca2+ Stores

2007 ◽  
Vol 76 (2) ◽  
pp. 857-862 ◽  
Author(s):  
Nelson O. Gekara ◽  
Lothar Groebe ◽  
Nuno Viegas ◽  
Siegfried Weiss
Keyword(s):  
Immune System ◽  
Listeria Monocytogenes ◽  
Calcium Signaling ◽  
Immune Cells ◽  
Prolonged Exposure ◽  
Cellular Responses ◽  
Host Cells ◽  
Listeriolysin O ◽  
Gram Positive Bacteria ◽  
Intracellular Ca

ABSTRACT Listeriolysin O (LLO), the pore-forming toxin of Listeria monocytogenes, is a prototype of the cholesterol-dependent cytolysins (CDCs) secreted by several pathogenic and nonpathogenic gram-positive bacteria. In addition to mediating the escape of the bacterium into the cytosol, this toxin is generally believed to be a central player in host-pathogen interactions during L. monocytogenes infection. LLO triggers the influx of Ca2+ into host cells as well as the release of Ca2+ from intracellular stores. Thus, many of the cellular responses induced by LLO are related to calcium signaling. Interestingly, in this study, we report that prolonged exposure to LLO desensitizes cells to Ca2+ mobilization upon subsequent stimulations with LLO. Cells preexposed to LLO-positive L. monocytogenes but not to the LLO-deficient Δhly mutant were found to be highly refractory to Ca2+ induction in response to receptor-mediated stimulation. Such cells also exhibited diminished Ca2+ signals in response to stimulation with LLO and thapsigargin. The presented results suggest that this phenomenon is due to the depletion of intracellular Ca2+ stores. The ability of LLO to desensitize immune cells provides a significant hint about the possible role played by CDCs in the evasion of the immune system by bacterial pathogens.

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