scholarly journals Immune Modulatory Short Noncoding RNAs Targeting the Glioblastoma Microenvironment

2021 ◽  
Vol 11 ◽  
Author(s):  
Jun Wei ◽  
Eli Gilboa ◽  
George A. Calin ◽  
Amy B. Heimberger
Keyword(s):  
Blood Brain Barrier ◽  
Immune Suppression ◽  
Immune Cells ◽  
Poor Prognosis ◽  
Immune Modulation ◽  
Antitumor Immunity ◽  
Noncoding Rnas ◽  
Delivery Vehicles ◽  
Immunosuppressive Microenvironment

Glioblastomas are heterogeneous and have a poor prognosis. Glioblastoma cells interact with their neighbors to form a tumor-permissive and immunosuppressive microenvironment. Short noncoding RNAs are relevant mediators of the dynamic crosstalk among cancer, stromal, and immune cells in establishing the glioblastoma microenvironment. In addition to the ease of combinatorial strategies that are capable of multimodal modulation for both reversing immune suppression and enhancing antitumor immunity, their small size provides an opportunity to overcome the limitations of blood-brain-barrier (BBB) permeability. To enhance glioblastoma delivery, these RNAs have been conjugated with various molecules or packed within delivery vehicles for enhanced tissue-specific delivery and increased payload. Here, we focus on the role of RNA therapeutics by appraising which types of nucleotides are most effective in immune modulation, lead therapeutic candidates, and clarify how to optimize delivery of the therapeutic RNAs and their conjugates specifically to the glioblastoma microenvironment.

scholarly journals Glioblastoma Immunotherapy Targeting the Innate Immune Checkpoint CD47-SIRPα Axis

2020 ◽  
Vol 11 ◽  
Author(s):  
Jinyang Hu ◽  
Qungen Xiao ◽  
Minhai Dong ◽  
Dongsheng Guo ◽  
Xudong Wu ◽  
...  
Keyword(s):  
T Cells ◽  
Poor Prognosis ◽  
Antitumor Immunity ◽  
Cytotoxic T Cells ◽  
Innate Immune ◽  
Intracranial Tumors ◽  
Aggressive Form ◽  
Limited Success ◽  
Immunosuppressive Microenvironment

Glioblastoma Multiforme (GBM) is the most common and aggressive form of intracranial tumors with poor prognosis. In recent years, tumor immunotherapy has been an attractive strategy for a variety of tumors. Currently, most immunotherapies take advantage of the adaptive anti-tumor immunity, such as cytotoxic T cells. However, the predominant accumulation of tumor-associated microglia/macrophages (TAMs) results in limited success of these strategies in the glioblastoma. To improve the immunotherapeutic efficacy for GBM, it is detrimental to understand the role of TAM in glioblastoma immunosuppressive microenvironment. In this review, we will discuss the roles of CD47-SIRPα axis in TAMs infiltration and activities and the promising effects of targeting this axis on the activation of both innate and adaptive antitumor immunity in glioblastoma.

scholarly journals Role of the Extracellular Traps in Central Nervous System

2021 ◽  
Vol 12 ◽  
Author(s):  
Xinyan Wu ◽  
Hanhai Zeng ◽  
Lingxin Cai ◽  
Gao Chen
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Blood Brain Barrier ◽  
Immune Cells ◽  
Brain Barrier ◽  
Extracellular Traps ◽  
Blood Brain ◽  
The Central Nervous System ◽  
Extracellular Trap

It has been reported that several immune cells can release chromatin and granular proteins into extracellular space in response to the stimulation, forming extracellular traps (ETs). The cells involved in the extracellular trap formation are recognized including neutropils, macrophages, basophils, eosinophils, and mast cells. With the development of research related to central nervous system, the role of ETs has been valued in neuroinflammation, blood–brain barrier, and other fields. Meanwhile, it has been found that microglial cells as the resident immune cells of the central nervous system can also release ETs, updating the original understanding. This review aims to clarify the role of the ETs in the central nervous system, especially in neuroinflammation and blood–brain barrier.

scholarly journals The role of oligosaccharides and polysaccharides of xylan and mannan in gut health of monogastric animals

2020 ◽  
Vol 9 ◽  
Author(s):  
Utsav P. Tiwari ◽  
Stephen A. Fleming ◽  
Muhammed S. Abdul Rasheed ◽  
R. Jha ◽  
Ryan N. Dilger
Keyword(s):  
Immune Responses ◽  
Immune Cells ◽  
Immune Modulation ◽  
The Body ◽  
Gut Health ◽  
Gi Tract ◽  
Immune Organ ◽  
Feed Ingredient ◽  
Cereal Grain

Abstract Apart from its role as a digestive and absorptive organ, the gastrointestinal (GI) tract is a vital immune organ that encompasses roughly 70 % of the total immune cells of the body. As such, the physical, chemical and nutrient composition of the diet influences overall GI function, effectively as an immune organ. With the improvement in feed technology, agro-industrial co-products that are high in fibre have been widely used as a feed ingredient in the diets of pigs and poultry. Arabinoxylan (AX) and mannan are the most abundant hemicellulosic polysaccharides present in cereal grain and co-product ingredients used in the livestock industry. When monogastric animals consume diets containing high amounts of AX and mannans, stimulation of GI immune cells may occur. This involves the activation of several cellular and molecular pathways of the immune system and requires a considerable amount of energy and nutrients to be expended by the animal, which may ultimately influence overall health and growth performance of animals. Therefore, a better understanding of the role of AX and mannan in immune modulation will be helpful in modulating untoward GI immune responses, thereby minimising nutrient and energy expenditure toward this effort. This review will summarise pertinent research on the role of oligosaccharides and polysaccharides containing AX and mannans in immune modulation in order to preserve gut integrity.

scholarly journals Role of specialized pro-resolving lipid mediators in pulmonary inflammation diseases: mechanisms and development

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Ailin Yang ◽  
Yanjun Wu ◽  
Ganggang Yu ◽  
Haoyan Wang
Keyword(s):  
Immune Cells ◽  
Immune Modulation ◽  
Respiratory Diseases ◽  
Preventive Measures ◽  
Pulmonary Inflammation ◽  
Lipid Mediators ◽  
Pulmonary Diseases ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease

AbstractInflammation is an essential mechanism of various diseases. The development and resolution of inflammation are complex immune-modulation processes which induce the involvement of various types of immune cells. Specialized pro-resolving lipid mediators (SPMs) have been demonstrated to be signaling molecules in inflammation. SPMs are involved in the pathophysiology of different diseases, especially respiratory diseases, including asthma, pneumonia, and chronic obstructive pulmonary disease. All of these diseases are related to the inflammatory response and its persistence. Therefore, a deeper understanding of the mechanisms and development of inflammation in respiratory disease, and the roles of the SPM family in the resolution process, might be useful in the quest for novel therapies and preventive measures for pulmonary diseases.

scholarly journals The Role of Trogocytosis in the Modulation of Immune Cell Functions

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1255
Author(s):  
Kensuke Miyake ◽  
Hajime Karasuyama
Keyword(s):  
Immune Cells ◽  
Immune Modulation ◽  
Immune Cell ◽  
Mhc Molecules ◽  
Cell Functions ◽  
Cell Extracts ◽  
Ligand Interactions ◽  
Molecule Interactions ◽  
Antigen Presenting

Trogocytosis is an active process, in which one cell extracts the cell fragment from another cell, leading to the transfer of cell surface molecules, together with membrane fragments. Recent reports have revealed that trogocytosis can modulate various biological responses, including adaptive and innate immune responses and homeostatic responses. Trogocytosis is evolutionally conserved from protozoan parasites to eukaryotic cells. In some cases, trogocytosis results in cell death, which is utilized as a mechanism for antibody-dependent cytotoxicity (ADCC). In other cases, trogocytosis-mediated intercellular protein transfer leads to both the acquisition of novel functions in recipient cells and the loss of cellular functions in donor cells. Trogocytosis in immune cells is typically mediated by receptor–ligand interactions, including TCR–MHC interactions and Fcγ receptor-antibody-bound molecule interactions. Additionally, trogocytosis mediates the transfer of MHC molecules to various immune and non-immune cells, which confers antigen-presenting activity on non-professional antigen-presenting cells. In this review, we summarize the recent advances in our understanding of the role of trogocytosis in immune modulation.

scholarly journals Small molecule AZD4635 inhibitor of A2AR signaling rescues immune cell function including CD103+ dendritic cells enhancing anti-tumor immunity

2020 ◽  
Vol 8 (2) ◽  
pp. e000417 ◽  
Author(s):  
Alexandra Borodovsky ◽  
Christine M Barbon ◽  
Yanjun Wang ◽  
Minwei Ye ◽  
Laura Prickett ◽  
...  
Keyword(s):  
T Cell ◽  
Antigen Presentation ◽  
Small Molecule ◽  
Immune Cells ◽  
Antitumor Immunity ◽  
Cell Function ◽  
Immune Cell ◽  
T Cell Function ◽  
Adenosine Signaling

Accumulation of extracellular adenosine within the microenvironment is a strategy exploited by tumors to escape detection by the immune system. Adenosine signaling through the adenosine 2A receptor (A2AR) on immune cells elicits a range of immunosuppressive effects which promote tumor growth and limit the efficacy of immune checkpoint inhibitors. Preclinical data with A2AR inhibitors have demonstrated tumor regressions in mouse models by rescuing T cell function; however, the mechanism and role on other immune cells has not been fully elucidated.MethodsWe report here the development of a small molecule A2AR inhibitor including characterization of binding and inhibition of A2AR function with varying amounts of a stable version of adenosine. Functional activity was tested in both mouse and human T cells and dendritic cells (DCs) in in vitro assays to understand the intrinsic role on each cell type. The role of adenosine and A2AR inhibition was tested in DC differentiation assays as well as co-culture assays to access the cross-priming function of DCs. Syngeneic models were used to assess tumor growth alone and in combination with alphaprogrammed death-ligand 1 (αPD-L1). Immunophenotyping by flow cytometry was performed to examine global immune cell changes upon A2AR inhibition.ResultsWe provide the first report of AZD4635, a novel small molecule A2AR antagonist which inhibits downstream signaling and increases T cell function as well as a novel mechanism of enhancing antigen presentation by CD103+ DCs. The role of antigen presentation by DCs, particularly CD103+ DCs, is critical to drive antitumor immunity providing rational to combine a priming agent AZD4635 with check point blockade. We find adenosine impairs the maturation and antigen presentation function of CD103+ DCs. We show in multiple syngeneic mouse tumor models that treatment of AZD4635 alone and in combination with αPD-L1 led to decreased tumor volume correlating with enhanced CD103+ function and T cell response. We extend these studies into human DCs to show that adenosine promotes a tolerogenic phenotype that can be reversed with AZD4635 restoring antigen-specific T cell activation. Our results support the novel role of adenosine signaling as an intrinsic negative regulator of CD103+ DCs maturation and priming. We show that potent inhibition of A2AR with AZD4635 reduces tumor burden and enhances antitumor immunity. This unique mechanism of action in CD103+ DCs may contribute to clinical responses as AZD4635 is being evaluated in clinical trials with IMFINZI (durvalumab, αPD-L1) in patients with solid malignancies.ConclusionWe provide evidence implicating suppression of adaptive and innate immunity by adenosine as a mechanism for immune evasion by tumors. Inhibition of adenosine signaling through selective small molecule inhibition of A2AR using AZD4635 restores T cell function via an internal mechanism as well as tumor antigen cross-presentation by CD103+ DCs resulting in antitumor immunity.

scholarly journals The role of lncRNAs and circRNAs in the PD-1/PD-L1 pathway in cancer immunotherapy

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Wenxiao Jiang ◽  
Shuya Pan ◽  
Xin Chen ◽  
Zhi-wei Wang ◽  
Xueqiong Zhu
Keyword(s):  
Cancer Immunotherapy ◽  
Tumor Cells ◽  
Antitumor Immunity ◽  
Immune Therapy ◽  
Noncoding Rnas ◽  
Immune Checkpoints ◽  
Circular Rnas ◽  
Antitumor Effects ◽  
Antitumor Immunotherapy

AbstractCancer immunotherapy has recently shown promising antitumor effects in various types of tumors. Among all immune checkpoints, the PD-1/PD-L1 pathway plays an important role in the immune evasion of tumor cells, making it a potent target in antitumor immunity. Accordingly, antibodies targeting the PD-1/PD-L1 pathway have been developed to attack tumor cells; however, resistance to immune therapy remains to be solved. Hence, identification of the underlying modulators of the PD-1/PD-L1 pathway is of significant importance to understand the mechanisms of antitumor immunotherapy. Long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) have been identified to regulate the PD-1/PD-L1 pathway, leading to participation in the immune response and immunotherapy. Therefore, this review focuses on the functions of lncRNAs and circRNAs in regulation of the PD-1/PD-L1 axis in tumorigenesis and tumor progression. We hope this review will stimulate research to supply more precise and effective cancer immune checkpoint therapies for a large number of tumors.

scholarly journals The Role of the Immune System in IBD-Associated Colorectal Cancer: From Pro to Anti-Tumorigenic Mechanisms

2021 ◽  
Vol 22 (23) ◽  
pp. 12739
Author(s):  
Sofía Frigerio ◽  
Dalia A. Lartey ◽  
Geert R. D’Haens ◽  
Joep Grootjans
Keyword(s):  
Colorectal Cancer ◽  
Immune System ◽  
Chronic Inflammation ◽  
Immune Cells ◽  
Checkpoint Inhibitors ◽  
Inflammatory Diseases ◽  
Cancer Development ◽  
Anti Inflammatory ◽  
Immunosuppressive Microenvironment

Patients with inflammatory bowel disease (IBD) have increased incidence of colorectal cancer (CRC). IBD-associated cancer follows a well-characterized sequence of intestinal epithelial changes, in which genetic mutations and molecular aberrations play a key role. IBD-associated cancer develops against a background of chronic inflammation and pro-inflammatory immune cells, and their products contribute to cancer development and progression. In recent years, the effect of the immunosuppressive microenvironment in cancer development and progression has gained more attention, mainly because of the unprecedented anti-tumor effects of immune checkpoint inhibitors in selected groups of patients. Even though IBD-associated cancer develops in the background of chronic inflammation which is associated with activation of endogenous anti-inflammatory or suppressive mechanisms, the potential role of an immunosuppressive microenvironment in these cancers is largely unknown. In this review, we outline the role of the immune system in promoting cancer development in chronic inflammatory diseases such as IBD, with a specific focus on the anti-inflammatory mechanisms and suppressive immune cells that may play a role in IBD-associated tumorigenesis.

scholarly journals Immunomodulation in Sepsis: The Role of Endotoxin Removal by Polymyxin B-Immobilized Cartridge

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Elisabeth Esteban ◽  
Ricard Ferrer ◽  
Laia Alsina ◽  
Antonio Artigas
Keyword(s):  
Severe Sepsis ◽  
Immune Cells ◽  
Immune Modulation ◽  
Polymyxin B ◽  
High Morbidity ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Immunological Mechanisms ◽  
Endotoxin Elimination

Severe sepsis results in high morbidity and mortality. Immunomodulation strategies could be an adjunctive therapy to treat sepsis. Endotoxin is a component of gram-negative bacteria and plays an important role in the pathogenesis of septic shock when it is recognized by immune cells. Removal of endotoxin could be an effective adjunctive approach to the management of sepsis. Devices to adsorb endotoxin or inflammatory cytokines have been designed as a strategy to treat severe sepsis, especially sepsis caused by gram-negative bacteria. Polymyxin B-immobilized cartridge has been successfully used to treat patients with sepsis of abdominal origin. Although this cartridge was conceived to adsorb endotoxin, several other immunological mechanisms have been elucidated, and this device has also yielded promising results in patients with nonseptic respiratory failure. In this paper, we summarize the immune modulation actions of Polymyxin B-immobilized cartridge to explore its potential usefulness beyond endotoxin elimination.

scholarly journals Long Noncoding RNA AC007639.1 Promotes the Pathogenesis and Progression of Hepatocellular Carcinoma Through Inhibiting Apoptosis and Stimulating Chemotherapeutic Resistance

2021 ◽  
Vol 11 ◽  
Author(s):  
Yun Bai ◽  
Meijuan Ding ◽  
Dan Lu ◽  
Yiwen Li ◽  
Shuai Yao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Noncoding Rna ◽  
Poor Prognosis ◽  
Noncoding Rnas ◽  
Xenograft Model ◽  
Xenograft Tumor ◽  
Mouse Xenograft ◽  
Cancer Cell Death ◽  
Resistance To Chemotherapy

BackgroundHepatocellular carcinoma (HCC) is known for its poor prognosis. Long noncoding RNAs (lncRNAs) are critical in the pathogenesis of various types of cancers. We tried to explore the role of lncRNA in the development of HCC.MethodsWe identified the role of lncRNA AC007639.1 in the pathogenesis of HCC through bioinformatics and biological experiments in HepG2, Hep3B, and SMMC-7721 cells as well as the nude mice xenograft model.ResultsWe found that lncRNA AC007639.1 was overexpressed in hepatocellular carcinoma. Knocking down of lncRNA AC007639.1 by specific siRNAs or shRNAs promoted cancer cell death. The growth of mouse xenograft tumor created using lncRNA AC007639.1 deficient HepG2 cells was significantly slowed down. Furthermore, the knockdown of lncRNA AC007639.1 in HCC cells led to the increased expression of p53 and decreased expression of angiopoietin-like 4.ConclusionLncRNA AC007639.1 was involved in the pathogenesis and progression of hepatocellular carcinoma by inhibition of apoptosis and increasing HCC resistance to chemotherapy.

Sign in / Sign up

Export Citation Format

Share Document