scholarly journals Programmed cell death-ligand 2: A neglected but important target in the immune response to cancer?

2020 ◽  
Vol 13 (10) ◽  
pp. 100811 ◽  
Author(s):  
Cinzia Solinas ◽  
Marco Aiello ◽  
Esdy Rozali ◽  
Matteo Lambertini ◽  
Karen Willard-Gallo ◽  
...  
Keyword(s):  
Immune Response ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Important Target ◽  
Immune Response To Cancer

scholarly journals Importance of the PD-1/PD-L1 Axis for Malignant Transformation and Risk Assessment of Oral Leukoplakia

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 194
Author(s):  
Jutta Ries ◽  
Abbas Agaimy ◽  
Falk Wehrhan ◽  
Christoph Baran ◽  
Stella Bolze ◽  
...  
Keyword(s):  
Immune Response ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Malignant Transformation ◽  
Immune Escape ◽  
Checkpoint Inhibitors ◽  
Precancerous Lesions ◽  
Death Receptor ◽  
Oral Leukoplakia ◽  
Significant Difference

Background: The programmed cell death ligand 1/programmed cell death receptor 1 (PD-L1/PD-1) Immune Checkpoint is an important modulator of the immune response. Overexpression of the receptor and its ligands is involved in immunosuppression and the failure of an immune response against tumor cells. PD-1/PD-L1 overexpression in oral squamous cell carcinoma (OSCC) compared to healthy oral mucosa (NOM) has already been demonstrated. However, little is known about its expression in oral precancerous lesions like oral leukoplakia (OLP). The aim of the study was to investigate whether an increased expression of PD-1/PD-L1 already exists in OLP and whether it is associated with malignant transformation. Material and Methods: PD-1 and PD-L1 expression was immunohistologically analyzed separately in the epithelium (E) and the subepithelium (S) of OLP that had undergone malignant transformation within 5 years (T-OLP), in OLP without malignant transformation (N-OLP), in corresponding OSCC and in NOM. Additionally, RT-qPCR analysis for PD-L1 expression was done in the entire tissues. Additionally, the association between overexpression and malignant transformation, dysplasia and inflammation were examined. Results: Compared to N-OLP, there were increased levels of PD-1 protein in the epithelial and subepithelial layers of T-OLP (pE = 0.001; pS = 0.005). There was no significant difference in PD-L1 mRNA expression between T-OLP and N-OLP (p = 0.128), but the fold-change increase between these groups was significant (Relative Quantification (RQ) = 3.1). In contrast to N-OLP, the PD-L1 protein levels were significantly increased in the epithelial layers of T-OLP (p = 0.007), but not in its subepithelial layers (p = 0.25). Importantly, increased PD-L1 levels were significantly associated to malignant transformation within 5 years. Conclusion: Increased levels of PD-1 and PD-L1 are related to malignant transformation in OLP and may represent a promising prognostic indicator to determine the risk of malignant progression of OLP. Increased PD-L1 levels might establish an immunosuppressive microenvironment, which could favor immune escape and thereby contribute to malignant transformation. Hence, checkpoint inhibitors could counteract tumor development in OLP and may serve as efficient therapeutic strategy in patients with high-risk precancerous lesions.

scholarly journals Myocardial Damage by SARS-CoV-2: Emerging Mechanisms and Therapies

Viruses ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1880
Author(s):  
Huyen Tran Ho ◽  
Stefan Peischard ◽  
Nathalie Strutz-Seebohm ◽  
Karin Klingel ◽  
Guiscard Seebohm
Keyword(s):  
Immune Response ◽  
Cell Death ◽  
Energy Metabolism ◽  
Programmed Cell Death ◽  
Viral Replication ◽  
Ion Homeostasis ◽  
Membrane Vesicles ◽  
Cardiac Cells ◽  
The Body ◽  
Double Membrane

Evidence is emerging that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can infect various organs of the body, including cardiomyocytes and cardiac endothelial cells in the heart. This review focuses on the effects of SARS-CoV-2 in the heart after direct infection that can lead to myocarditis and an outline of potential treatment options. The main points are: (1) Viral entry: SARS-CoV-2 uses specific receptors and proteases for docking and priming in cardiac cells. Thus, different receptors or protease inhibitors might be effective in SARS-CoV-2-infected cardiac cells. (2) Viral replication: SARS-CoV-2 uses RNA-dependent RNA polymerase for replication. Drugs acting against ssRNA(+) viral replication for cardiac cells can be effective. (3) Autophagy and double-membrane vesicles: SARS-CoV-2 manipulates autophagy to inhibit viral clearance and promote SARS-CoV-2 replication by creating double-membrane vesicles as replication sites. (4) Immune response: Host immune response is manipulated to evade host cell attacks against SARS-CoV-2 and increased inflammation by dysregulating immune cells. Efficiency of immunosuppressive therapy must be elucidated. (5) Programmed cell death: SARS-CoV-2 inhibits programmed cell death in early stages and induces apoptosis, necroptosis, and pyroptosis in later stages. (6) Energy metabolism: SARS-CoV-2 infection leads to disturbed energy metabolism that in turn leads to a decrease in ATP production and ROS production. (7) Viroporins: SARS-CoV-2 creates viroporins that lead to an imbalance of ion homeostasis. This causes apoptosis, altered action potential, and arrhythmia.

Combination of DNA demethylation and chemotherapy to trigger cell pyroptosis for inhalation treatment of lung cancer

Nanoscale ◽  
2021 ◽  
Author(s):  
Beibei Xie ◽  
Tingting Liu ◽  
Shuang Chen ◽  
Yan Zhang ◽  
Dongxian He ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Immune Response ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Effective Means ◽  
Dna Demethylation ◽  
Local Immune Response ◽  
Anticancer Efficacy

Pyroptosis is an inflammation-dependent and self-cascade amplifying type of programmed cell death, serving as an effective means for activating the local immune response and improving the anticancer efficacy. As the...

scholarly journals Maprotiline Prompt the Anti-tumor Effect by Inhibiting the PD-L1 in Mice Burdened Melanoma

2021 ◽  
Author(s):  
Tiesuo Zhao ◽  
Yang Li ◽  
Miaomiao Liu ◽  
Lin Zhou ◽  
Zunge Wu ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Tumor Tissues ◽  
Programmed Cell Death 1 ◽  
Tetracyclic Antidepressant ◽  
And Migration ◽  
Cell Death Protein

Abstract Programmed cell death 1 ligand 1(PD-L1) binds with programmed cell death protein 1 (PD-1) to inhibit the responses of T cells. PD-L1 is significantly upregulated on tumor cells and blocking the PD-L1/PD-1 signal has become an important target of immunotherapy in clinic. At present, some old drugs of non-antitumor have been found that could play the effect of anti-tumor. Maprotiline, as a tetracyclic antidepressant, has been widely used for treating mental depression. Here, we study the anti-tumor effect of maprotiline by strengthening the immune response of mice. In vitro, treatment with maprotiline inhibits the proliferation and migration of B16 cells, increases the cell apoptosis. Importantly, treatment with maprotiline reduces the expression of PD-L1 in tumor tissue, prompts the ratios of CD4+ T cells, CD8+ T cells and NK cells in spleens, increases the infiltration of CD4+ and CD8+ T cells in tumor-tissues. In brief, we determine that maprotiline could prompt the anti-tumor immune response by inhibiting the PD-L1 in mice. This study may find a new inhibitor of PD-L1, which provides a new drug treated tumor in clinical.

scholarly journals Molecular Modeling Studies on the Binding Mode of the PD-1/PD-L1 Complex Inhibitors

2019 ◽  
Vol 20 (18) ◽  
pp. 4654
Author(s):  
Suliman Almahmoud ◽  
Haizhen A. Zhong
Keyword(s):  
Cell Death ◽  
Molecular Docking ◽  
Programmed Cell Death ◽  
Ligand Binding ◽  
Binding Mode ◽  
Docking Studies ◽  
Important Target ◽  
Molecular Modeling Studies ◽  
L1 Protein ◽  
Cell Death Protein

The programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) is an immune checkpoint (ICP) overexpressed in various types of tumors; thus, it has been considered as an important target for cancer therapy. To determine important residues for ligand binding, we applied molecular docking studies to PD-1/PD-L1 complex inhibitors against the PD-L1 protein. Our data revealed that the residues Tyr56, Asp122, and Lys124 play critical roles in ligand binding to the PD-L1 protein and they could be used to design ligands that are active against the PD-1/PD-L1 complex. The formation of H-bonds with Arg125 of the PD-L1 protein may enhance the potency of the PD-1/PD-L1 binding.

scholarly journals RBM15-mediated N6-methyladenosine modification affects COVID-19 severity by regulating the expression of multitarget genes

2021 ◽  
Vol 12 (8) ◽  
Author(s):  
Yuting Meng ◽  
Qiong Zhang ◽  
Kaihang Wang ◽  
Xujun Zhang ◽  
Rongwei Yang ◽  
...  
Keyword(s):  
Immune Response ◽  
Cell Death ◽  
Severe Acute Respiratory Syndrome ◽  
Programmed Cell Death ◽  
Inflammatory Response ◽  
Disease Severity ◽  
Biological Processes ◽  
Underlying Mechanisms ◽  
Microarray Analyses

AbstractSevere coronavirus disease 2019 (COVID-19) is characterized by symptoms of lymphopenia and multiorgan damage, but the underlying mechanisms remain unclear. To explore the function of N6-methyladenosine (m6A) modifications in COVID-19, we performed microarray analyses to comprehensively characterize the m6A epitranscriptome. The results revealed distinct global m6A profiles in severe and mild COVID-19 patients. Programmed cell death and inflammatory response were the major biological processes modulated by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Further, RBM15, a major m6A methyltransferase, was significantly elevated and positively correlated with disease severity. Silencing RBM15 drastically reduced lymphocyte death in vitro. Knockdown of RBM15 remarkably suppressed the expression levels of multitarget genes related to programmed cell death and inflammatory response. This study shows that SARS-CoV-2 infection alters the m6A epitranscriptome of lymphocytes, particularly in the case of severe patients. RBM15 regulated host immune response to SARS-CoV-2 by elevating m6A modifications of multitarget genes. These findings indicate that RBM15 can serve as a target for the treatment of COVID-19.

Innate immune response and programmed cell death following carrier-mediated delivery of unmodified mRNA to respiratory cells

2013 ◽  
Vol 167 (2) ◽  
pp. 157-166 ◽  
Author(s):  
Oliwia Andries ◽  
Marina De Filette ◽  
Stefaan C. De Smedt ◽  
Jo Demeester ◽  
Mario Van Poucke ◽  
...  
Keyword(s):  
Immune Response ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Innate Immune Response ◽  
Innate Immune ◽  
Respiratory Cells
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