scholarly journals Regulation of Adaptive Tumor Immunity by Non-Coding RNAs

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5651
Author(s):  
Eleftheria Papaioannou ◽  
María del Pilar González-Molina ◽  
Ana M. Prieto-Muñoz ◽  
Laura Gámez-Reche ◽  
Alicia González-Martín
Keyword(s):  
Immune Responses ◽  
Cancer Immunotherapy ◽  
Tumor Immunity ◽  
Immune Cell ◽  
Protein Coding ◽  
Protein Coding Genes ◽  
Therapeutic Value ◽  
Non Coding Rnas ◽  
And Function

Cancer immunology research has mainly focused on the role of protein-coding genes in regulating immune responses to tumors. However, despite more than 70% of the human genome is transcribed, less than 2% encodes proteins. Many non-coding RNAs (ncRNAs), including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), have been identified as critical regulators of immune cell development and function, suggesting that they might play important roles in orchestrating immune responses against tumors. In this review, we summarize the scientific advances on the role of ncRNAs in regulating adaptive tumor immunity, and discuss their potential therapeutic value in the context of cancer immunotherapy.

Dietary and Physiological Effects of Zinc on the Immune System

2021 ◽  
Vol 41 (1) ◽  
Author(s):  
Inga Wessels ◽  
Henrike Josephine Fischer ◽  
Lothar Rink
Keyword(s):  
Immune Responses ◽  
Immune Cells ◽  
Immune Cell ◽  
Current Knowledge ◽  
Annual Review ◽  
Publication Date ◽  
Biological Processes ◽  
And Function ◽  
Broad Overview

Evidence for the importance of zinc for all immune cells and for mounting an efficient and balanced immune response to various environmental stressors has been accumulating in recent years. This article describes the role of zinc in fundamental biological processes and summarizes our current knowledge of zinc's effect on hematopoiesis, including differentiation into immune cell subtypes. In addition, the important role of zinc during activation and function of immune cells is detailed and associated with the specific immune responses to bacteria, parasites, and viruses. The association of zinc with autoimmune reactions and cancers as diseases with increased or decreased immune responses is also discussed. This article provides a broad overview of the manifold roles that zinc, or its deficiency, plays in physiology and during various diseases. Consequently, we discuss why zinc supplementation should be considered, especially for people at risk of deficiency. Expected final online publication date for the Annual Review of Nutrition, Volume 41 is September 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals MicroRNAs: immune modulators in cancer immunotherapy

2021 ◽  
Author(s):  
Yun Xing ◽  
Zhiqiang Wang ◽  
Zhou Lu ◽  
Jie Xia ◽  
Zhangjuan Xie ◽  
...  
Keyword(s):  
Immune Responses ◽  
Cancer Immunotherapy ◽  
Tumor Cells ◽  
Tumor Immunity ◽  
Immune Cells ◽  
Tumor Suppressors ◽  
Immune Modulators ◽  
Non Coding Rna ◽  
New Findings

Abstract MicroRNA (miRNA) is a class of endogenous small non-coding RNA of 18–25 nucleotides and plays regulatory roles in both physiological and pathological processes. Emerging evidence support that miRNAs function as immune modulators in tumors. MiRNAs as tumor suppressors or oncogenes are also found to be able to modulate anti-tumor immunity or link the crosstalk between tumor cells and immune cells surrounding. Based on the specific regulating function, miRNAs can be used as predictive, prognostic biomarkers and therapeutic targets in immunotherapy. Here, we review new findings about role of miRNAs in modulating immune responses, as well as discuss mechanisms underlying their dysregulation, and their clinical potentials as indicators of tumor prognosis or to sensitize cancer immunotherapy.

Long non-coding RNAs and splicing

2021 ◽  
Author(s):  
David Staněk
Keyword(s):  
Dominant Role ◽  
Splice Sites ◽  
Protein Coding ◽  
Protein Coding Genes ◽  
Non Coding Rna ◽  
Splicing Efficiency ◽  
Non Coding Rnas ◽  
Intron Removal ◽  
Long Non Coding Rna

Abstract In this review I focus on the role of splicing in long non-coding RNA (lncRNA) life. First, I summarize differences between the splicing efficiency of protein-coding genes and lncRNAs and discuss why non-coding RNAs are spliced less efficiently. In the second half of the review, I speculate why splice sites are the most conserved sequences in lncRNAs and what additional roles could splicing play in lncRNA metabolism. I discuss the hypothesis that the splicing machinery can, besides its dominant role in intron removal and exon joining, protect cells from undesired transcripts.

Enforced Expression Of Mir-125b Promotes the in vivo expansion Of Human Linneg cord Blood Multi-Lymphoid Progenitors and Leukemia Stem Cells

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1648-1648
Author(s):  
Karin G. Hermans ◽  
Eric R. Lechman ◽  
Stephanie M. Dobson ◽  
Mark D. Minden ◽  
John E. Dick
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Fold Increase ◽  
Control Vector ◽  
Self Renewal ◽  
Protein Coding ◽  
Protein Coding Genes ◽  
Non Coding Rnas

Abstract Acute Myeloid Leukemia (AML) is a heterogeneous disease with a relapse rate of up to 80% depending on patient age and AML subtype. AML is organized as a functional cellular hierarchy and is sustained by a rare population of leukemia stem cells (LSC). Recent work suggests that LSC properties influence therapy response, overall survival, and disease relapse. In order to develop more effective novel therapies that target this rare cell population; it is imperative that we better understand LSCs at the molecular level. Although it is generally accepted that oncogenic mutations underlie cancer initiation and progression, most studies have focused on protein coding genes. However, there is increasing recognition that non-coding RNAs can also play a role in leukemogenesis. microRNAs (miRNA) are a family of small non-coding RNAs that function as important regulators of mRNA stability and translation of protein-coding genes with significant roles in maintenance of human hematopoietic stem cells (HSC) (Lechman et. al., Cell Stem Cell, 2012). To understand the functional role of miRNA in human hematopoiesis, we generated HSC- and leukemia stem cell (LSC)-specific microRNA (miRNA) profiles by microarray analysis of sorted cell fractions from umbilical cord blood (CB) and AML patient samples that have been validated in xenograft assays. We identified ten miRNA candidates over-represented in HSC and/or LSC. To determine whether these were functional and impacted on stem cell properties we transduced lineage depleted CB cells with lentivirus expressing either a candidate miRNA or control vector followed by transplantation into immune deficient mice. Three miRNAs (miR-125b, miR-130a, miR-155) conferred a competitive growth advantage while four miRNAs (miR-99a, miR133a, miR194, miR-196b) conferred a growth disadvantage. miR-125b, a top LSC array candidate, showed the most pronounced phenotype with an overt expansion of transduced cells (19% to 96.2%) and enlarged spleens (2.4 fold increase). Detailed flow cytometric analysis of the miR-125b human grafts in recipient mice revealed a greatly expanded proportion of multi-lymphoid progenitors (MLP), in comparison to HSC and multi-potent progenitors. Furthermore, upon enforced in vivo expression of miR-125b in three AML patient samples, we observed large increases in the primitive primitive CD34+CD117+ populations (CD34+: 2.4-4.6 fold increase; CD117+: 1.3-4.1 fold increase) and a decrease in the proportion of differentiated CD14+/CD15+ cells (CD14+: 6.2-7.6 fold decrease; CD15+: 1.2-6 fold decrease) in leukemic grafts. Limiting dilution assays into secondary recipients revealed up to a 34-fold increase in LSC frequency compared to control vector transduced AML cells. Overall, these data suggest that miR-125b normally functions in the limited self-renewal of lymphoid committed early progenitors and this function may be usurped during leukemogenesis to enhance LSC self-renewal. miR-125b belongs to an evolutionarily conserved family consisting of three paralogs (miR-125a; miR-125b1; miR-125b2). Recent studies present strong evidence for a role of the miR-125 family in normal and malignant murine hematopoiesis, yet comprehensive functional inconsistencies remain in regards to the precise roles for each paralog. We are currently carrying out additional enforced expression studies directly comparing these family members in vitro and in vivo in order to clarify the functional roles of miR-125a (a top HSC array candidate) and miR-125b (a top LSC array candidate) in both normal and malignant human hematopoiesis. These studies will determine whether the miR-125 family is a suitable target for therapy of hematological malignancies. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Role of Pseudogenes in Tumorigenesis

Cancers ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 256 ◽  
Author(s):  
Xinling Hu ◽  
Liu Yang ◽  
Yin-Yuan Mo
Keyword(s):  
Critical Role ◽  
Cellular Functions ◽  
Protein Coding ◽  
Master Regulators ◽  
Protein Coding Genes ◽  
The Past ◽  
High Sequence Homology ◽  
Regulation Mechanisms ◽  
Non Coding Rnas

Functional genomics has provided evidence that the human genome transcribes a large number of non-coding genes in addition to protein-coding genes, including microRNAs and long non-coding RNAs (lncRNAs). Among the group of lncRNAs are pseudogenes that have not been paid attention in the past, compared to other members of lncRNAs. However, increasing evidence points the important role of pseudogenes in diverse cellular functions, and dysregulation of pseudogenes are often associated with various human diseases including cancer. Like other types of lncRNAs, pseudogenes can also function as master regulators for gene expression and thus, they can play a critical role in various aspects of tumorigenesis. In this review we discuss the latest developments in pseudogene research, focusing on how pseudogenes impact tumorigenesis through different gene regulation mechanisms. Given the high sequence homology with the corresponding parent genes, we also discuss challenges for pseudogene research.

scholarly journals Comprehensive Review on the Clinical Relevance of Long Non-Coding RNAs in Cutaneous Melanoma

2021 ◽  
Vol 22 (3) ◽  
pp. 1166
Author(s):  
Vincenzo De Falco ◽  
Stefania Napolitano ◽  
Daniela Esposito ◽  
Luigi Pio Guerrera ◽  
Davide Ciardiello ◽  
...  
Keyword(s):  
Cutaneous Melanoma ◽  
Acquired Resistance ◽  
Protein Coding ◽  
Rna Transcripts ◽  
Protein Coding Genes ◽  
Different Types ◽  
Fine Regulation ◽  
Non Coding Rnas ◽  
Different Tissues

Cutaneous melanoma is considered a rare tumor, although it is one of the most common cancers in young adults and its incidence has risen in the last decades. Targeted therapy, with BRAF and MEK inhibitors, and immunotherapy revolutionized the treatment of metastatic melanoma but there is still a considerable percentage of patients with primary or acquired resistance to these therapies. Recently, oncology researchers directed their attention at the role of long non-coding RNAs (lncRNAs) in different types of cancers, including melanoma. lncRNAs are RNA transcripts, initially considered “junk sequences”, that have been proven to have a crucial role in the fine regulation of physiological and pathological processes of different tissues. Furthermore, they are more expressed in tumors than protein-coding genes, constituting perfect candidates either as biomarkers (diagnostic, prognostic, predictive) or as therapeutic targets. In this work, we reviewed all the literature available for lncRNA in melanoma, elucidating all the potential roles in this tumor.

scholarly journals Mechanistic Roles of Noncoding RNAs in Lung Cancer Biology and Their Clinical Implications

2012 ◽  
Vol 2012 ◽  
pp. 1-16 ◽  
Author(s):  
Katey S. S. Enfield ◽  
Larissa A. Pikor ◽  
Victor D. Martinez ◽  
Wan L. Lam
Keyword(s):  
Lung Cancer ◽  
Rna Splicing ◽  
Cancer Biology ◽  
Noncoding Rnas ◽  
Protein Coding ◽  
Cellular Processes ◽  
Protein Coding Genes ◽  
Non Coding Rnas ◽  
Clinical Potential

Lung cancer biology has traditionally focused on genomic and epigenomic deregulation of protein-coding genes to identify oncogenes and tumor suppressors diagnostic and therapeutic targets. Another important layer of cancer biology has emerged in the form of noncoding RNAs (ncRNAs), which are major regulators of key cellular processes such as proliferation, RNA splicing, gene regulation, and apoptosis. In the past decade, microRNAs (miRNAs) have moved to the forefront of ncRNA cancer research, while the role of long noncoding RNAs (lncRNAs) is emerging. Here we review the mechanisms by which miRNAs and lncRNAs are deregulated in lung cancer, the technologies that can be applied to detect such alterations, and the clinical potential of these RNA species. An improved comprehension of lung cancer biology will come through the understanding of the interplay between deregulation of non-coding RNAs, the protein-coding genes they regulate, and how these interactions influence cellular networks and signalling pathways.

scholarly journals Non-Coding RNAs as Prognostic Markers for Endometrial Cancer

2021 ◽  
Vol 22 (6) ◽  
pp. 3151 ◽  
Author(s):  
Roberto Piergentili ◽  
Simona Zaami ◽  
Anna Franca Cavaliere ◽  
Fabrizio Signore ◽  
Giovanni Scambia ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Prognostic Markers ◽  
Classification Systems ◽  
Prognostic Role ◽  
Protein Coding ◽  
Pathological Characteristics ◽  
Epigenetic Events ◽  
Cancer Types ◽  
Non Coding Rnas

Endometrial cancer (EC) has been classified over the years, for prognostic and therapeutic purposes. In recent years, classification systems have been emerging not only based on EC clinical and pathological characteristics but also on its genetic and epigenetic features. Noncoding RNAs (ncRNAs) are emerging as promising markers in several cancer types, including EC, for which their prognostic value is currently under investigation and will likely integrate the present prognostic tools based on protein coding genes. This review aims to underline the importance of the genetic and epigenetic events in the EC tumorigenesis, by expounding upon the prognostic role of ncRNAs.

scholarly journals 114 Preclinical development of a novel iPSC-derived CAR-MICA/B NK cell immunotherapy to overcome solid tumor escape from NKG2D-mediated mechanisms of recognition and killing

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A126-A126
Author(s):  
John Goulding ◽  
Mochtar Pribadi ◽  
Robert Blum ◽  
Wen-I Yeh ◽  
Yijia Pan ◽  
...  
Keyword(s):  
T Cells ◽  
Cancer Immunotherapy ◽  
Tumor Immunity ◽  
Immune Cell ◽  
Nk Cell ◽  
Tumor Escape ◽  
Car T Cells ◽  
Car T

BackgroundMHC class I related proteins A (MICA) and B (MICB) are induced by cellular stress and transformation, and their expression has been reported for many cancer types. NKG2D, an activating receptor expressed on natural killer (NK) and T cells, targets the membrane-distal domains of MICA/B, activating a potent cytotoxic response. However, advanced cancer cells frequently evade immune cell recognition by proteolytic shedding of the α1 and α2 domains of MICA/B, which can significantly reduce NKG2D function and the cytolytic activity.MethodsRecent publications have shown that therapeutic antibodies targeting the membrane-proximal α3 domain inhibited MICA/B shedding, resulting in a substantial increase in the cell surface density of MICA/B and restoration of immune cell-mediated tumor immunity.1 We have developed a novel chimeric antigen receptor (CAR) targeting the conserved α3 domain of MICA/B (CAR-MICA/B). Additionally, utilizing our proprietary induced pluripotent stem cell (iPSC) product platform, we have developed multiplexed engineered, iPSC-derived CAR-MICA/B NK (iNK) cells for off-the-shelf cancer immunotherapy.ResultsA screen of CAR spacer and ScFv orientations in primary T cells delineated MICA-specific in vitro activation and cytotoxicity as well as in vivo tumor control against MICA+ cancer cells. The novel CAR-MICA/B design was used to compare efficacy against NKG2D CAR T cells, an alternative MICA/B targeting strategy. CAR-MICA/B T cells showed superior cytotoxicity against melanoma, breast cancer, renal cell carcinoma, and lung cancer lines in vitro compared to primary NKG2D CAR T cells (p<0.01). Additionally, using an in vivo xenograft metastasis model, CAR-MICA/B T cells eliminated A2058 human melanoma metastases in the majority of the mice treated. In contrast, NKG2D CAR T cells were unable to control tumor growth or metastases. To translate CAR-MICA/B functionality into an off-the-shelf cancer immunotherapy, CAR-MICA/B was introduced into a clonal master engineered iPSC line to derive a multiplexed engineered, CAR-MICA/B iNK cell product candidate. Using a panel of tumor cell lines expressing MICA/B, CAR-MICA/B iNK cells displayed MICA specificity, resulting in enhanced cytokine production, degranulation, and cytotoxicity. Furthermore, in vivo NK cell cytotoxicity was evaluated using the B16-F10 melanoma cell line, engineered to express MICA. In this model, CAR-MICA/B iNK cells significantly reduced liver and lung metastases, compared to untreated controls, by 93% and 87% respectively.ConclusionsOngoing work is focused on extending these preclinical studies to further support the clinical translation of an off-the-shelf, CAR-MICA/B iNK cell cancer immunotherapy with the potential to overcome solid tumor escape from NKG2D-mediated mechanisms of recognition and killing.ReferenceFerrari de Andrade L, Tay RE, Pan D, Luoma AM, Ito Y, Badrinath S, Tsoucas D, Franz B, May KF Jr, Harvey CJ, Kobold S, Pyrdol JW, Yoon C, Yuan GC, Hodi FS, Dranoff G, Wucherpfennig KW. Antibody-mediated inhibition of MICA and MICB shedding promotes NK cell-driven tumor immunity. Science 2018 Mar 30;359(6383):1537–1542.

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