scholarly journals Long Non-Coding RNAs (lncRNAs) in Response and Resistance to Cancer Immunosurveillance and Immunotherapy

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3313
Author(s):  
Giasemi C. Eptaminitaki ◽  
Nora Wolff ◽  
Dimitris Stellas ◽  
Konstantinos Sifakis ◽  
Stavroula Baritaki
Keyword(s):  
Immune Cells ◽  
Molecular Mechanisms ◽  
Immune Cell ◽  
Immune Escape ◽  
Regulatory Elements ◽  
Cellular Functions ◽  
Cancer Immunity ◽  
Immune Mediated ◽  
Non Coding Rnas ◽  
Cancer Immunosurveillance

Long non-coding RNAs (lncRNAs) are critical regulatory elements in cellular functions in states of both normalcy and disease, including cancer. LncRNAs can influence not only tumorigenesis but also cancer features such as metastasis, angiogenesis and resistance to chemo-and immune-mediated apoptotic signals. Several lncRNAs have been demonstrated to control directly or indirectly the number, type and activities of distinct immune cell populations of adaptive and innate immunities within and without the tumor microenvironment. The disruption of lncRNA expression in both cancer and immune cells may reflect alterations in tumor responses to cancer immunosurveillance and immunotherapy, thus providing new insights into lncRNA biomarker-based prognostic and therapeutic cancer assessment. Here we present an overview on lncRNAs’ functions and underlying molecular mechanisms related to cancer immunity and conventional immunotherapy, with the expectation that any elucidations may lead to a better understanding and management of cancer immune escape and response to current and future immunotherapeutics.

scholarly journals A Novel Regulatory Player in the Innate Immune System: Long Non-Coding RNAs

2021 ◽  
Vol 22 (17) ◽  
pp. 9535
Author(s):  
Yuhuai Xie ◽  
Yuanyuan Wei
Keyword(s):  
Immune System ◽  
Immune Cells ◽  
Innate Immune System ◽  
Molecular Mechanisms ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Immune Mediated ◽  
Development And Differentiation ◽  
Non Coding Rnas ◽  
And Function

Long non-coding RNAs (lncRNAs) represent crucial transcriptional and post-transcriptional gene regulators during antimicrobial responses in the host innate immune system. Studies have shown that lncRNAs are expressed in a highly tissue- and cell-specific- manner and are involved in the differentiation and function of innate immune cells, as well as inflammatory and antiviral processes, through versatile molecular mechanisms. These lncRNAs function via the interactions with DNA, RNA, or protein in either cis or trans pattern, relying on their specific sequences or their transcriptions and processing. The dysregulation of lncRNA function is associated with various human non-infectious diseases, such as inflammatory bowel disease, cardiovascular diseases, and diabetes mellitus. Here, we provide an overview of the regulation and mechanisms of lncRNA function in the development and differentiation of innate immune cells, and during the activation or repression of innate immune responses. These elucidations might be beneficial for the development of therapeutic strategies targeting inflammatory and innate immune-mediated diseases.

The Intersection of Metformin and Inflammation

2021 ◽  
Author(s):  
Leena P. Bharath ◽  
Barbara S. Nikolajczyk
Keyword(s):  
Mitochondrial Function ◽  
Immune Cells ◽  
Immune Cell ◽  
Cell Types ◽  
Remarkable Effect ◽  
Tumor Onset ◽  
Age Related ◽  
Immune Mediated ◽  
Autoimmune Conditions ◽  
Near Term

The biguanide metformin is the most commonly used antidiabetic drug. Recent studies show that metformin not only improves chronic inflammation by improving metabolic parameters but also has a direct anti-inflammatory effect. In light of these findings, it is essential to identify the inflammatory pathways targeted by metformin to develop a comprehensive understanding of the mechanisms of action of this drug. Commonly accepted mechanisms of metformin action include AMPK activation and inhibition of mTOR pathways, which are evaluated in multiple diseases. Additionally, metformin's action on mitochondrial function and cellular homeostasis processes such as autophagy, is of particular interest because of the importance of these mechanisms in maintaining cellular health. Both dysregulated mitochondria and failure of the autophagy pathways, the latter of which impair clearance of dysfunctional, damaged, or excess organelles, affect cellular health drastically and can trigger the onset of metabolic and age-related diseases. Immune cells are the fundamental cell types that govern the health of an organism. Thus, dysregulation of autophagy or mitochondrial function in immune cells has a remarkable effect on susceptibility to infections, response to vaccination, tumor onset, and the development of inflammatory and autoimmune conditions. Here we summarize the latest research on metformin's regulation of immune cell mitochondrial function and autophagy as evidence that new clinical trials on metformin with primary outcomes related to the immune system should be considered to treat immune-mediated diseases over the near term.

scholarly journals Tuning cancer fate: the unremitting role of host immunity

Open Biology ◽  
2017 ◽  
Vol 7 (4) ◽  
pp. 170006 ◽  
Author(s):  
B. Calì ◽  
B. Molon ◽  
A. Viola
Keyword(s):  
Immune Cells ◽  
Immune Cell ◽  
Tumour Progression ◽  
Host Immunity ◽  
Adaptive Immune ◽  
Adaptive Immune Cells ◽  
Immune Mediated ◽  
Immune Cell Subsets ◽  
Therapeutic Protocols

Host immunity plays a central and complex role in dictating tumour progression. Solid tumours are commonly infiltrated by a large number of immune cells that dynamically interact with the surrounding microenvironment. At first, innate and adaptive immune cells successfully cooperate to eradicate microcolonies of transformed cells. Concomitantly, surviving tumour clones start to proliferate and harness immune responses by specifically hijacking anti-tumour effector mechanisms and fostering the accumulation of immunosuppressive immune cell subsets at the tumour site. This pliable interplay between immune and malignant cells is a relentless process that has been concisely organized in three different phases: elimination, equilibrium and escape. In this review, we aim to depict the distinct immune cell subsets and immune-mediated responses characterizing the tumour landscape throughout the three interconnected phases. Importantly, the identification of key immune players and molecules involved in the dynamic crosstalk between tumour and immune system has been crucial for the introduction of reliable prognostic factors and effective therapeutic protocols against cancers.

scholarly journals Molecular mechanisms governing circulating immune cell heterogeneity across different species revealed by single cell sequencing

2021 ◽  
Author(s):  
Zhibin Li ◽  
chengcheng Sun ◽  
Fei Wang ◽  
Xiran Wang ◽  
Jiacheng Zhu ◽  
...  
Keyword(s):  
Single Cell ◽  
Immune Cells ◽  
Evolutionary Biology ◽  
Regulatory Networks ◽  
Molecular Mechanisms ◽  
Mononuclear Cells ◽  
Immune Cell ◽  
Cell Types ◽  
Genetic Regulatory Networks ◽  
Peripheral Blood Mononuclear

Background: Immune cells play important roles in mediating immune response and host defense against invading pathogens. However, insights into the molecular mechanisms governing circulating immune cell diversity among multiple species are limited. Methods: In this study, we compared the single-cell transcriptomes of 77 957 immune cells from 12 species using single-cell RNA-sequencing (scRNA-seq). Distinct molecular profiles were characterized for different immune cell types, including T cells, B cells, natural killer cells, monocytes, and dendritic cells. Results: The results revealed the heterogeneity and compositions of circulating immune cells among 12 different species. Additionally, we explored the conserved and divergent cellular cross-talks and genetic regulatory networks among vertebrate immune cells. Notably, the ligand and receptor pair VIM-CD44 was highly conserved among the immune cells. Conclusions: This study is the first to provide a comprehensive analysis of the cross-species single-cell atlas for peripheral blood mononuclear cells (PBMCs). This research should advance our understanding of the cellular taxonomy and fundamental functions of PBMCs, with important implications in evolutionary biology, developmental biology, and immune system disorders

scholarly journals Long noncoding RNA: a dazzling dancer in tumor immune microenvironment

2020 ◽  
Vol 39 (1) ◽  
Author(s):  
Yalu Zhang ◽  
Qiaofei Liu ◽  
Quan Liao
Keyword(s):  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Immune Escape ◽  
Noncoding Rnas ◽  
Pathological Process ◽  
Cellular Functions ◽  
Immune Microenvironment ◽  
Protein Coding ◽  
Functional Roles ◽  
Tumor Immune Microenvironment

Abstract Long noncoding RNAs (lncRNAs) are a class of endogenous, non-protein coding RNAs that are highly linked to various cellular functions and pathological process. Emerging evidence indicates that lncRNAs participate in crosstalk between tumor and stroma, and reprogramming of tumor immune microenvironment (TIME). TIME possesses distinct populations of myeloid cells and lymphocytes to influence the immune escape of cancer, the response to immunotherapy, and the survival of patients. However, hitherto, a comprehensive review aiming at relationship between lncRNAs and TIME is missing. In this review, we focus on the functional roles and molecular mechanisms of lncRNAs within the TIME. Furthermore, we discussed the potential immunotherapeutic strategies based on lncRNAs and their limitations.

scholarly journals Unveiling the immune infiltrate modulation in cancer and response to immunotherapy by MIXTURE—an enhanced deconvolution method

2020 ◽  
Author(s):  
Elmer A Fernández ◽  
Yamil D Mahmoud ◽  
Florencia Veigas ◽  
Darío Rocha ◽  
Matías Miranda ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Immune Cells ◽  
Immune Cell ◽  
Immune Escape ◽  
Intratumor Heterogeneity ◽  
Support Vector ◽  
Tumor Immune Escape ◽  
Immune Infiltrate ◽  
Tumor Biopsies

Abstract The accurate quantification of tumor-infiltrating immune cells turns crucial to uncover their role in tumor immune escape, to determine patient prognosis and to predict response to immune checkpoint blockade. Current state-of-the-art methods that quantify immune cells from tumor biopsies using gene expression data apply computational deconvolution methods that present multicollinearity and estimation errors resulting in the overestimation or underestimation of the diversity of infiltrating immune cells and their quantity. To overcome such limitations, we developed MIXTURE, a new ν-support vector regression-based noise constrained recursive feature selection algorithm based on validated immune cell molecular signatures. MIXTURE provides increased robustness to cell type identification and proportion estimation, outperforms the current methods, and is available to the wider scientific community. We applied MIXTURE to transcriptomic data from tumor biopsies and found relevant novel associations between the components of the immune infiltrate and molecular subtypes, tumor driver biomarkers, tumor mutational burden, microsatellite instability, intratumor heterogeneity, cytolytic score, programmed cell death ligand 1 expression, patients’ survival and response to anti-cytotoxic T-lymphocyte-associated antigen 4 and anti-programmed cell death protein 1 immunotherapy.

scholarly journals The Emerging Role of Long Non-Coding RNAs in Plant Defense Against Fungal Stress

2020 ◽  
Vol 21 (8) ◽  
pp. 2659
Author(s):  
Hong Zhang ◽  
Huan Guo ◽  
Weiguo Hu ◽  
Wanquan Ji
Keyword(s):  
Stress Responses ◽  
Higher Plants ◽  
Regulatory Elements ◽  
Cellular Functions ◽  
Non Coding Rna ◽  
Non Coding Rnas ◽  
Resistance To Infection ◽  
Regulatory Functions ◽  
Long Non Coding Rna

Growing interest and recent evidence have identified long non-coding RNA (lncRNA) as the potential regulatory elements for eukaryotes. LncRNAs can activate various transcriptional and post-transcriptional events that impact cellular functions though multiple regulatory functions. Recently, a large number of lncRNAs have also been identified in higher plants, and an understanding of their functional role in plant resistance to infection is just emerging. Here, we focus on their identification in crop plant, and discuss their potential regulatory functions and lncRNA-miRNA-mRNA network in plant pathogen stress responses, referring to possible examples in a model plant. The knowledge gained from a deeper understanding of this colossal special group of plant lncRNAs will help in the biotechnological improvement of crops.

scholarly journals Genetic associations at regulatory phenotypes improve fine-mapping of causal variants for twelve immune-mediated diseases

2020 ◽  
Author(s):  
Kousik Kundu ◽  
Alice L. Mann ◽  
Manuel Tardaguila ◽  
Stephen Watt ◽  
Hannes Ponstingl ◽  
...  
Keyword(s):  
Fine Mapping ◽  
Molecular Mechanisms ◽  
Immune Cell ◽  
Meta Analysis ◽  
Cell Types ◽  
Genetic Associations ◽  
Sequencing Data ◽  
Immune Mediated ◽  
Causal Genes ◽  
Causal Variants

AbstractThe identification of causal genetic variants for common diseases improves understanding of disease biology. Here we use data from the BLUEPRINT project to identify regulatory quantitative trait loci (QTL) for three primary human immune cell types and use these to fine-map putative causal variants for twelve immune-mediated diseases. We identify 340 unique, non major histocompatibility complex (MHC) disease loci that colocalise with high (>98%) posterior probability with regulatory QTLs, and apply Bayesian frameworks to fine-map associations at each locus. We show that fine-mapping applied to regulatory QTLs yields smaller credible set sizes and higher posterior probabilities for candidate causal variants compared to disease summary statistics. We also describe a systematic under-representation of insertion/deletion (INDEL) polymorphisms in credible sets derived from publicly available disease meta-analysis when compared to QTLs based on genome-sequencing data. Overall, our findings suggest that fine-mapping applied to disease-colocalising regulatory QTLs can enhance the discovery of putative causal disease variants and provide insights into the underlying causal genes and molecular mechanisms.

scholarly journals New Pharmacological Tools to Target Leukocyte Trafficking in Lung Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Kylie B. R. Belchamber ◽  
Michael J. Hughes ◽  
Daniella A. Spittle ◽  
Eloise M. Walker ◽  
Elizabeth Sapey
Keyword(s):  
Lung Disease ◽  
Immune Cells ◽  
Lung Diseases ◽  
Immune Cell ◽  
Current Evidence ◽  
Chronic Obstructive ◽  
Cellular Functions ◽  
Obstructive Pulmonary Disease ◽  
Microbial Invasion ◽  
Infection And Inflammation

Infection and inflammation of the lung results in the recruitment of non-resident immune cells, including neutrophils, eosinophils and monocytes. This swift response should ensure clearance of the threat and resolution of stimuli which drive inflammation. However, once the threat is subdued this influx of immune cells should be followed by clearance of recruited cells through apoptosis and subsequent efferocytosis, expectoration or retrograde migration back into the circulation. This cycle of cell recruitment, containment of threat and then clearance of immune cells and repair is held in exquisite balance to limit host damage. Advanced age is often associated with detrimental changes to the balance described above. Cellular functions are altered including a reduced ability to traffic accurately towards inflammation, a reduced ability to clear pathogens and sustained inflammation. These changes, seen with age, are heightened in lung disease, and most chronic and acute lung diseases are associated with an exaggerated influx of immune cells, such as neutrophils, to the airways as well as considerable inflammation. Indeed, across many lung diseases, pathogenesis and progression has been associated with the sustained presence of trafficking cells, with examples including chronic diseases such as Chronic Obstructive Pulmonary Disease and Idiopathic Pulmonary Fibrosis and acute infections such as Pneumonia and Pneumonitis. In these instances, there is evidence that dysfunctional and sustained recruitment of cells to the airways not only increases host damage but impairs the hosts ability to effectively respond to microbial invasion. Targeting leukocyte migration in these instances, to normalise cellular responses, has therapeutic promise. In this review we discuss the current evidence to support the trafficking cell as an immunotherapeutic target in lung disease, and which potential mechanisms or pathways have shown promise in early drug trials, with a focus on the neutrophil, as the quintessential trafficking immune cell.

scholarly journals Pathological alteration and therapeutic implications of sepsis-induced immune cell apoptosis

2019 ◽  
Vol 10 (10) ◽  
Author(s):  
Chao Cao ◽  
Muming Yu ◽  
Yanfen Chai
Keyword(s):  
Inflammatory Response ◽  
Immune Cells ◽  
Cell Apoptosis ◽  
Molecular Mechanisms ◽  
Immune Cell ◽  
Specific Treatment ◽  
Treatment Modalities ◽  
Initial State ◽  
Adaptive Immune Cells ◽  
Secondary Infections

Abstract Sepsis is a life-threatening organ dysfunction syndrome caused by dysregulated host response to infection that leads to uncontrolled inflammatory response followed by immunosuppression. However, despite the high mortality rate, no specific treatment modality or drugs with high efficacy is available for sepsis to date. Although improved treatment strategies have increased the survival rate during the initial state of excessive inflammatory response, recent trends in sepsis show that mortality occurs at a period of continuous immunosuppressive state in which patients succumb to secondary infections within a few weeks or months due to post-sepsis “immune paralysis.” Immune cell alteration induced by uncontrolled apoptosis has been considered a major cause of significant immunosuppression. Particularly, apoptosis of lymphocytes, including innate immune cells and adaptive immune cells, is associated with a higher risk of secondary infections and poor outcomes. Multiple postmortem studies have confirmed that sepsis-induced immune cell apoptosis occurs in all age groups, including neonates, pediatric, and adult patients, and it is considered to be a primary contributing factor to the immunosuppressive pathophysiology of sepsis. Therapeutic perspectives targeting apoptosis through various strategies could improve survival in sepsis. In this review article, we will focus on describing the major apoptosis process of immune cells with respect to physiologic and molecular mechanisms. Further, advances in apoptosis-targeted treatment modalities for sepsis will also be discussed.

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