scholarly journals What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 3: PD-L1, Intracellular Signaling Pathways and Tumor Microenvironment

2021 ◽  
Vol 22 (22) ◽  
pp. 12330
Author(s):  
Andrea Palicelli ◽  
Stefania Croci ◽  
Alessandra Bisagni ◽  
Eleonora Zanetti ◽  
Dario De Biase ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Tumor Microenvironment ◽  
Literature Review ◽  
Signaling Pathways ◽  
Systematic Literature Review ◽  
Immune Cells ◽  
Intracellular Signaling ◽  
Immune Escape ◽  
Tumor Immune Escape ◽  
Intracellular Signaling Pathways

The tumor microenvironment (TME) includes immune (T, B, NK, dendritic), stromal, mesenchymal, endothelial, adipocytic cells, extracellular matrix, and cytokines/chemokines/soluble factors regulating various intracellular signaling pathways (ISP) in tumor cells. TME influences the survival/progression of prostate cancer (PC), enabling tumor cell immune-evasion also through the activation of the PD-1/PD-L1 axis. We have performed a systematic literature review according to the PRISMA guidelines, to investigate how the PD-1/PD-L1 pathway is influenced by TME and ISPs. Tumor immune-escape mechanisms include suppression/exhaustion of tumor infiltrating cytotoxic T lymphocytes, inhibition of tumor suppressive NK cells, increase in immune-suppressive immune cells (regulatory T, M2 macrophagic, myeloid-derived suppressor, dendritic, stromal, and adipocytic cells). IFN-γ (the most investigated factor), TGF-β, TNF-α, IL-6, IL-17, IL-15, IL-27, complement factor C5a, and other soluble molecules secreted by TME components (and sometimes increased in patients’ serum), as well as and hypoxia, influenced the regulation of PD-L1. Experimental studies using human and mouse PC cell lines (derived from either androgen-sensitive or androgen-resistant tumors) revealed that the intracellular ERK/MEK, Akt-mTOR, NF-kB, WNT and JAK/STAT pathways were involved in PD-L1 upregulation in PC. Blocking the PD-1/PD-L1 signaling by using immunotherapy drugs can prevent tumor immune-escape, increasing the anti-tumor activity of immune cells.

scholarly journals Collapsing the list of myocardial infarction-related differential expressed genes into a diagnostic signature

2020 ◽  
Author(s):  
German Osmak ◽  
Natalia Baulina ◽  
Philipp Koshkin ◽  
Olga Favorova
Keyword(s):  
Myocardial Infarction ◽  
Signaling Pathways ◽  
Immune Cells ◽  
Intracellular Signaling ◽  
Mononuclear Cells ◽  
Learning Algorithm ◽  
Classification Model ◽  
Central Component ◽  
Intracellular Signaling Pathways ◽  
Differential Expressed Genes

AbstractMyocardial infarction (MI) is one of the most severe manifestations of coronary artery disease (CAD) and the leading cause of death from non-infectious diseases worldwide. It is known that the central component of CAD pathogenesis is a chronic vascular inflammation. However, the mechanisms underlying the changes that occur in T, B and NK lymphocytes, monocytes and other immune cells during CAD and MI are still poorly understood. One of those pathogenic mechanisms might be the dysregulation of intracellular signaling pathways in the immune cells.In the present study we performed a transcriptome profiling in peripheral blood mononuclear cells of MI patients and controls. The machine learning algorithm was then used to search for MI-associated signatures, that could reflect the dysregulation of intracellular signaling pathways.The genes ADAP2, KLRC1, MIR21, PDGFD and CD14 were identified as the most important signatures for the classification model with L1-norm penalty function. The classifier output quality was equal to 0.911 by Receiver Operating Characteristic metric on test data. These results were validated on two independent open GEO datasets. Identified MI-associated signatures can be further assisted in MI diagnosis and/or prognosis.Thus, our study presents a pipeline for collapsing the list of differential expressed genes, identified by high-throughput techniques, in order to define disease-associated diagnostic signatures.

scholarly journals Cartilage and Bone Destruction in Arthritis: Pathogenesis and Treatment Strategy: A Literature Review

Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 818 ◽  
Author(s):  
Tateiwa ◽  
Yoshikawa ◽  
Kaito
Keyword(s):  
Rheumatoid Arthritis ◽  
Signaling Pathways ◽  
Immune Cells ◽  
Intracellular Signaling ◽  
Bone Destruction ◽  
Therapeutic Strategies ◽  
Intracellular Signaling Pathways ◽  
Extracellular Signaling ◽  
Intracellular Signals ◽  
Novel Therapeutic

Arthritis is inflammation of the joints accompanied by osteochondral destruction. It can take many forms, including osteoarthritis, rheumatoid arthritis, and psoriatic arthritis. These diseases share one commonality—osteochondral destruction based on inflammation. The background includes a close interaction between osseous tissues and immune cells through various inflammatory cytokines. However, the tissues and cytokines that play major roles are different in each disease, and as a result, the mechanism of osteochondral destruction also differs. In recent years, there have been many findings regarding not only extracellular signaling pathways but also intracellular signaling pathways. In particular, we anticipate that the intracellular signals of osteoclasts, which play a central role in bone destruction, will become novel therapeutic targets. In this review, we have summarized the pathology of arthritis and the latest findings on the mechanism of osteochondral destruction, as well as present and future therapeutic strategies for these targets.

scholarly journals Exosomes Derived from RM-1 Cells Promote the Recruitment of MDSCs into Tumor Microenvironment by Upregulating CXCR4 via TLR2/NF- κ B Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Nan Li ◽  
Yingying Wang ◽  
Haoyu Xu ◽  
Hexi Wang ◽  
Yingying Gao ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Flow Cytometry ◽  
Tumor Microenvironment ◽  
Immune Escape ◽  
Critical Role ◽  
Specific Inhibitor ◽  
Signalling Pathway ◽  
Dependent Manner ◽  
Migration Ability ◽  
Tumor Immune Escape

Myeloid-derived suppressor cells (MDSCs) play a critical role in tumor immune escape because of its remarkable immunosuppressive effect. However, the mechanism of MDSCs migrated into tumor microenvironment remains unclear. In this study, we demonstrated the recruitment of MDSCs can be promoted by exosomes derived from prostate cancer cells, which could upregulate chemokine (CXC motif) receptor 4 (CXCR4) via the TLR2/NF- κ B signalling pathway. Flow cytometry detected that the percentage of MDSCs in the mice spleen and tumor tissue was significantly increased after injection with exosomes via mouse tail vein. Transwell chemotaxis assay showed the recruitment of MDSCs toward the lower chamber was enhanced after stimulation with exosomes, and the migration ability could be inhibited by AMD3100 (a CXCR4 specific inhibitor) both in vivo and in vitro. Additionally, Western blot and flow cytometry verified a remarkably increase of CXCR4 in MDSCs after incubation with exosomes; meanwhile, the protein level of TLR2 and activation of NF- κ B were also strengthened obviously. Nevertheless, after blocking TLR2 by C29 (a TLR2-specific inhibitor), the expression of p-p65 and CXCR4, which were hypothesized as the downstream target of TLR2, was prominently reduced. In conclusion, prostate cancer-derived exosomes could reinforce CXCR4 expression in MDSCs through the TLR2/NF- κ B signalling pathway, eventually promoting migration of MDSCs into tumor microenvironment in a CXCR4-CXCL12 axis-dependent manner.

scholarly journals Targeted Glucose or Glutamine Metabolic Therapy Combined With PD-1/PD-L1 Checkpoint Blockade Immunotherapy for the Treatment of Tumors - Mechanisms and Strategies

2021 ◽  
Vol 11 ◽  
Author(s):  
Guofeng Ma ◽  
Chun Li ◽  
Zhilei Zhang ◽  
Ye Liang ◽  
Zhijuan Liang ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Immune Cells ◽  
Immune Escape ◽  
Tumor Therapy ◽  
Checkpoint Blockade ◽  
Metabolic Reprogramming ◽  
Glutamine Metabolism ◽  
Tumor Immune Escape ◽  
New Era ◽  
Cell Expression

Immunotherapy, especially PD-1/PD-L1 checkpoint blockade immunotherapy, has led tumor therapy into a new era. However, the vast majority of patients do not benefit from immunotherapy. One possible reason for this lack of response is that the association between tumors, immune cells and metabolic reprogramming in the tumor microenvironment affect tumor immune escape. Generally, the limited amount of metabolites in the tumor microenvironment leads to nutritional competition between tumors and immune cells. Metabolism regulates tumor cell expression of PD-L1, and the PD-1/PD-L1 immune checkpoint regulates the metabolism of tumor and T cells, which suggests that targeted tumor metabolism may have a synergistic therapeutic effect together with immunotherapy. However, the targeting of different metabolic pathways in different tumors may have different effects on tumor immune escape. Herein, we discuss the influence of glucose metabolism and glutamine metabolism on tumor immune escape and describe the theoretical basis for strategies targeting glucose or glutamine metabolism in combination with PD-1/PD-L1 checkpoint blockade immunotherapy.

scholarly journals Interaction of dual intracellular signaling pathways activated by the melanocortin-3 receptor.

1994 ◽  
Vol 269 (18) ◽  
pp. 13162-13166
Author(s):  
Y. Konda ◽  
I. Gantz ◽  
J. DelValle ◽  
Y. Shimoto ◽  
H. Miwa ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Intracellular Signaling ◽  
Intracellular Signaling Pathways
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