scholarly journals The CD70-CD27 axis in oncology: the new kids on the block

2022 ◽  
Vol 41 (1) ◽  
Author(s):  
Tal Flieswasser ◽  
Astrid Van den Eynde ◽  
Jonas Van Audenaerde ◽  
Jorrit De Waele ◽  
Filip Lardon ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Immune Responses ◽  
Hematological Malignancies ◽  
Expression Patterns ◽  
Therapeutic Strategies ◽  
Physiological Conditions ◽  
Solid Malignancies ◽  
Checkpoint Molecule ◽  
Novel Target

AbstractThe immune checkpoint molecule CD70 and its receptor CD27 are aberrantly expressed in many hematological and solid malignancies. Dysregulation of the CD70-CD27 axis within the tumor and its microenvironment is associated with tumor progression and immunosuppression. This is in contrast to physiological conditions, where tightly controlled expression of CD70 and CD27 plays a role in co-stimulation in immune responses. In hematological malignancies, cancer cells co-express CD70 and CD27 promoting stemness, proliferation and survival of malignancy. In solid tumors, only expression of CD70 is present on the tumor cells which can facilitate immune evasion through CD27 expression in the tumor microenvironment. The discovery of these tumor promoting and immunosuppressive effects of the CD70-CD27 axis has unfolded a novel target in the field of oncology, CD70.In this review, we thoroughly discuss current insights into expression patterns and the role of the CD70-CD27 axis in hematological and solid malignancies, its effect on the tumor microenvironment and (pre)clinical therapeutic strategies.

scholarly journals The Inflammatory Chemokine CCL5 and Cancer Progression

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Donatella Aldinucci ◽  
Alfonso Colombatti
Keyword(s):  
Cell Proliferation ◽  
Tumor Microenvironment ◽  
Cancer Progression ◽  
Hematological Malignancies ◽  
Therapeutic Strategies ◽  
Cancer Cell Proliferation ◽  
Inflammatory Chemokines ◽  
Immunosuppressive Microenvironment ◽  
Receptor Ccr5

Until recently, inflammatory chemokines were viewed mainly as indispensable “gate keepers” of immunity and inflammation. However, updated research indicates that cancer cells subvert the normal chemokine system and these molecules and their receptors become important constituents of the tumor microenvironment with very different ways to exert tumor-promoting roles. The CCR5 and the CCL5 ligand have been detected in some hematological malignancies, lymphomas, and a great number of solid tumors, but extensive studies on the role of the CCL5/CCR axis were performed only in a limited number of cancers. This review summarizes updated information on the role of CCL5 and its receptor CCR5 in cancer cell proliferation, metastasis, and the formation of an immunosuppressive microenvironment and highlights the development of newer therapeutic strategies aimed to inhibit the binding of CCL5 to CCR5, to inhibit CCL5 secretion, or to inhibit the interactions among tumor cells and the microenvironment leading to CCL5 secretion.

scholarly journals Plasma Membrane Calcium ATPase Regulates Stoichiometry of CD4+ T-Cell Compartments

2021 ◽  
Vol 12 ◽  
Author(s):  
Maylin Merino-Wong ◽  
Barbara A. Niemeyer ◽  
Dalia Alansary
Keyword(s):  
Plasma Membrane ◽  
T Cell ◽  
Immune Responses ◽  
Chromatin Immunoprecipitation ◽  
Expression Patterns ◽  
Calcium Atpase ◽  
Cd4 T Cell ◽  
Plasma Membrane Calcium Atpase ◽  
Cell Compartments

Immune responses involve mobilization of T cells within naïve and memory compartments. Tightly regulated Ca2+ levels are essential for balanced immune outcomes. How Ca2+ contributes to regulating compartment stoichiometry is unknown. Here, we show that plasma membrane Ca2+ ATPase 4 (PMCA4) is differentially expressed in human CD4+ T compartments yielding distinct store operated Ca2+ entry (SOCE) profiles. Modulation of PMCA4 yielded a more prominent increase of SOCE in memory than in naïve CD4+ T cell. Interestingly, downregulation of PMCA4 reduced the effector compartment fraction and led to accumulation of cells in the naïve compartment. In silico analysis and chromatin immunoprecipitation point towards Ying Yang 1 (YY1) as a transcription factor regulating PMCA4 expression. Analyses of PMCA and YY1 expression patterns following activation and of PMCA promoter activity following downregulation of YY1 highlight repressive role of YY1 on PMCA expression. Our findings show that PMCA4 adapts Ca2+ levels to cellular requirements during effector and quiescent phases and thereby represent a potential target to intervene with the outcome of the immune response.

scholarly journals The ST2/Interleukin-33 Axis in Hematologic Malignancies: The IL-33 Paradox

2019 ◽  
Vol 20 (20) ◽  
pp. 5226 ◽  
Author(s):  
Alessandro Allegra ◽  
Vanessa Innao ◽  
Gennaro Tartarisco ◽  
Giovanni Pioggia ◽  
Marco Casciaro ◽  
...  
Keyword(s):  
Immune Responses ◽  
Myeloid Leukemia ◽  
Hematological Malignancies ◽  
Cell Damage ◽  
Hematologic Malignancies ◽  
Positive Role ◽  
Interleukin 33 ◽  
Relevant Role ◽  
Negative Role

Interleukin (IL)-33 is a chromatin-related nuclear interleukin that is a component of IL-1 family. IL-33 production augments the course of inflammation after cell damage or death. It is discharged into the extracellular space. IL-33 is regarded as an “alarmin” able to stimulate several effectors of the immune system, regulating numerous immune responses comprising cancer immune reactions. IL-33 has been demonstrated to influence tumorigenesis. However, as far as this cytokine is concerned, we are faced with what has sometimes been defined as the IL-33 paradox. Several studies have demonstrated a relevant role of IL-33 to numerous malignancies, where it may have pro- and—less frequently—antitumorigenic actions. In the field of hematological malignancies, the role of IL-33 seems even more complex. Although we can affirm the existence of a negative role of IL-33 in Chronic myelogenos leukemia (CML) and in lymphoproliferative diseases and a positive role in pathologies such as Acute myeloid leukemia (AML), the action of IL-33 seems to be multiple and sometimes contradictory within the same pathology. In the future, we will have to learn to govern the negative aspects of activating the IL-33/ST2 axis and exploit the positive ones.

scholarly journals Sendai Virus Infection Induces Expression of Novel RNAs in Human Cells

2018 ◽  
Author(s):  
Roli Mandhana ◽  
Curt M. Horvath
Keyword(s):  
Immune Responses ◽  
Sendai Virus ◽  
Expression Patterns ◽  
Sequence Conservation ◽  
Gene Repertoire ◽  
Direct Stimulation ◽  
Herpes Simplex Virus 1 ◽  
Protein Coding ◽  
Novel Target ◽  
Simplex Virus

Innate antiviral immune responses are driven by virus-induced changes in host gene expression. While much research on antiviral effectors has focused on virus-inducible mRNAs, recent genome-wide analyses have identified hundreds of novel target sites for virus-inducible transcription factors and RNA polymerase. These sites are beyond the known antiviral gene repertoire and their contribution to innate immune responses is largely unknown. In this study, RNA-sequencing of mock-infected and Sendai virus-infected cells was performed to characterize the virus-inducible transcriptome and identify novel virus-inducible RNAs (nviRNAs). Virus-inducible transcription was observed throughout the genome resulting in expression of 1755 previously RefSeq-annotated RNAs and 1545 nviRNAs. The previously-annotated RNAs primarily consist of protein-coding mRNAs, including several well-known antiviral mRNAs that had low sequence conservation but were highly virus-inducible. The previously-unannotated nviRNAs were mostly noncoding RNAs with poor sequence conservation. Independent analyses of nviRNAs based on infection with Sendai virus, influenza virus, and herpes simplex virus 1, or direct stimulation with IFNα revealed a range of expression patterns in various human cell lines. These phylogenetic and expression analyses suggest that many of the nviRNAs share the high inducibility and low sequence conservation characteristic of well-known primary antiviral effectors and may represent dynamically evolving antiviral factors.

scholarly journals Epigenetic Reprogramming of CD4+ Helper T Cells as a Strategy to Improve Anticancer Immunotherapy

2021 ◽  
Vol 12 ◽  
Author(s):  
Elodie Renaude ◽  
Marie Kroemer ◽  
Christophe Borg ◽  
Paul Peixoto ◽  
Eric Hervouet ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Microenvironment ◽  
Immune Responses ◽  
Antitumor Immunity ◽  
Epigenetic Reprogramming ◽  
Helper T Cells ◽  
Epigenetic Factors ◽  
Epigenetic Drugs ◽  
Anticancer Immunotherapy

Evidences highlight the role of various CD4+ helper T cells (CD4+ Th) subpopulations in orchestrating the immune responses against cancers. Epigenetics takes an important part in the regulation of CD4+ Th polarization and plasticity. In this review, we described the epigenetic factors that govern CD4+ T cells differentiation and recruitment in the tumor microenvironment and their subsequent involvement in the antitumor immunity. Finally, we discussed how to manipulate tumor reactive CD4+ Th responses by epigenetic drugs to improve anticancer immunotherapy.

scholarly journals HMGA Proteins in Hematological Malignancies

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1456
Author(s):  
Angela Minervini ◽  
Nicoletta Coccaro ◽  
Luisa Anelli ◽  
Antonella Zagaria ◽  
Giorgina Specchia ◽  
...  
Keyword(s):  
Chromatin Remodeling ◽  
Dna Sequences ◽  
Transcriptional Activity ◽  
Hematological Malignancies ◽  
High Mobility ◽  
Neoplastic Transformation ◽  
Therapeutic Strategies ◽  
Transcriptional Activators ◽  
Chromatin Modeling

The high mobility group AT-Hook (HMGA) proteins are a family of nonhistone chromatin remodeling proteins known as “architectural transcriptional factors”. By binding the minor groove of AT-rich DNA sequences, they interact with the transcription apparatus, altering the chromatin modeling and regulating gene expression by either enhancing or suppressing the binding of the more usual transcriptional activators and repressors, although they do not themselves have any transcriptional activity. Their involvement in both benign and malignant neoplasias is well-known and supported by a large volume of studies. In this review, we focus on the role of the HMGA proteins in hematological malignancies, exploring the mechanisms through which they enhance neoplastic transformation and how this knowledge could be exploited to devise tailored therapeutic strategies.

scholarly journals WNT and β-Catenin in Cancer: Genes and Therapy

2020 ◽  
Vol 4 (1) ◽  
pp. 177-196 ◽  
Author(s):  
Rene Jackstadt ◽  
Michael Charles Hodder ◽  
Owen James Sansom
Keyword(s):  
Tumor Microenvironment ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Wnt Pathway ◽  
Therapeutic Strategy ◽  
Wnt Signaling Pathway ◽  
Therapeutic Strategies ◽  
Tissue Homeostasis ◽  
Cancer Genes

The WNT pathway is a pleiotropic signaling pathway that controls developmental processes, tissue homeostasis, and cancer. The WNT pathway is commonly mutated in many cancers, leading to widespread research into the role of WNT signaling in carcinogenesis. Understanding which cancers are reliant upon WNT activation and which components of the WNT signaling pathway are mutated is paramount to advancing therapeutic strategies. In addition, building holistic insights into the role of WNT signaling in not only tumor cells but also the tumor microenvironment is a vital area of research and may be a promising therapeutic strategy in multiple immunologically inert cancers. Novel compounds aimed at modulating the WNT signaling pathway using diverse mechanisms are currently under investigation in preclinical/early clinical studies. Here, we review how the WNT pathway is activated in multiple cancers and discuss current strategies to target aberrant WNT signaling.

scholarly journals The role of cytokines in the processes of adaptive integration of immune and neuroendocrine reactions of the human body

2021 ◽  
Vol 67 (2) ◽  
pp. 4-9
Author(s):  
E. A. Troshina
Keyword(s):  
Immune Responses ◽  
Therapeutic Strategies ◽  
Main Task ◽  
Combined Effects ◽  
Immune Stimulation ◽  
Adaptive Integration ◽  
The Subject ◽  
To Receive ◽  
The Brain

The immune, endocrine and nervous systems are integrated due to the existence of reciprocal pathways for transmitting information about changes in their actual functional state. The main task of the brain is to receive, integrate and store information, and there is strong evidence that this also applies to information obtained through the body’s immune responses. It has been proven that the production of cytokines in the brain can be caused not only by peripheral immune stimulation, but also by the nerve cells themselves, stimulated by certain neurosensory signals. Evolutionarily preserved antihomeostatic mechanisms characteristic of specific diseases are the subject of further research, the results of which may be very important for the development of therapeutic strategies that would prevent the undesirable combined effects of immune and neuroendocrine mediators.

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