scholarly journals ERK is a Pivotal Player of Chemo-Immune-Resistance in Cancer

2019 ◽  
Vol 20 (10) ◽  
pp. 2505 ◽  
Author(s):  
Iris C. Salaroglio ◽  
Eleonora Mungo ◽  
Elena Gazzano ◽  
Joanna Kopecka ◽  
Chiara Riganti
Keyword(s):  
Immune System ◽  
Cancer Cells ◽  
Immune Escape ◽  
Erk Signaling ◽  
Host Immune System ◽  
Immune Resistance ◽  
Survival Pathways ◽  
Extracellular Signal ◽  
Pros And Cons ◽  
And Migration

The extracellular signal-related kinases (ERKs) act as pleiotropic molecules in tumors, where they activate pro-survival pathways leading to cell proliferation and migration, as well as modulate apoptosis, differentiation, and senescence. Given its central role as sensor of extracellular signals, ERK transduction system is widely exploited by cancer cells subjected to environmental stresses, such as chemotherapy and anti-tumor activity of the host immune system. Aggressive tumors have a tremendous ability to adapt and survive in stressing and unfavorable conditions. The simultaneous resistance to chemotherapy and immune system responses is common, and ERK signaling plays a key role in both types of resistance. In this review, we dissect the main ERK-dependent mechanisms and feedback circuitries that simultaneously determine chemoresistance and immune-resistance/immune-escape in cancer cells. We discuss the pros and cons of targeting ERK signaling to induce chemo-immune-sensitization in refractory tumors.

scholarly journals The Role of Sphingolipids in Cancer Immunotherapy

2021 ◽  
Vol 22 (12) ◽  
pp. 6492
Author(s):  
Paola Giussani ◽  
Alessandro Prinetti ◽  
Cristina Tringali
Keyword(s):  
Immune System ◽  
Cancer Cells ◽  
Immune Cells ◽  
Plasma Membranes ◽  
Checkpoint Inhibitors ◽  
Surface Receptors ◽  
Car T ◽  
Sphingosine 1 Phosphate ◽  
And Migration ◽  
Lymphocyte Egress

Immunotherapy is now considered an innovative and strong strategy to beat metastatic, drug-resistant, or relapsing tumours. It is based on the manipulation of several mechanisms involved in the complex interplay between cancer cells and immune system that culminates in a form of immune-tolerance of tumour cells, favouring their expansion. Current immunotherapies are devoted enforcing the immune response against cancer cells and are represented by approaches employing vaccines, monoclonal antibodies, interleukins, checkpoint inhibitors, and chimeric antigen receptor (CAR)-T cells. Despite the undoubted potency of these treatments in some malignancies, many issues are being investigated to amplify the potential of application and to avoid side effects. In this review, we discuss how sphingolipids are involved in interactions between cancer cells and the immune system and how knowledge in this topic could be employed to enhance the efficacy of different immunotherapy approaches. In particular, we explore the following aspects: how sphingolipids are pivotal components of plasma membranes and could modulate the functionality of surface receptors expressed also by immune cells and thus their functionality; how sphingolipids are related to the release of bioactive mediators, sphingosine 1-phosphate, and ceramide that could significantly affect lymphocyte egress and migration toward the tumour milieu, in addition regulating key pathways needed to activate immune cells; given the renowned capability of altering sphingolipid expression and metabolism shown by cancer cells, how it is possible to employ sphingolipids as antigen targets.

scholarly journals WISP2 promotes cell proliferation via targeting ERK and YAP in ovarian cancer cells

2020 ◽  
Author(s):  
Zi-Qing Shi ◽  
Zi-Yan Chen ◽  
Yao Han ◽  
Heng-Yan Zhu ◽  
Meng-Dan Lyu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Inhibitory Effect ◽  
Ovarian Cancer Cells ◽  
Growth Inhibitory ◽  
Extracellular Signal ◽  
And Migration

Abstract Background Wnt inducible signaling protein 2 (WISP2) is a wnt1-induced signaling pathway protein 2. Although studies indicate that WISP2 may promote the development of various tumors, its role in ovarian cancer remains unclear. The objective of the current study was to analyze the effects of WISP2 on proliferation and migration of ovarian cancer cells in vitro and in vivo . Results Immunohistochemistry and western blot results indicated that WISP2 was highly expressed in various ovarian tissues and cell lines. WISP2 deletion inhibited cell growth, clone formation, and migration of ovarian cancer cells. WISP2 deletion promoted cell apoptosis and affected the cell cycle. This growth inhibitory effect caused by WISP2 loss is due to the inhibition of extracellular signal-related kinase (p-ERK)1/2, as well as CEBPα and CEBPβ. In addition, WISP2 deletion also activated the Yes-associated protein (YAP). Conclusion WISP2 deletion inhibits ovarian cancer cell proliferation by affecting ERK signaling pathways.

scholarly journals Glances in Immunology of HIV and HCV Infection

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Maria Giovanna Quaranta ◽  
Benedetta Mattioli ◽  
Stefano Vella
Keyword(s):  
Immune System ◽  
Immune Escape ◽  
Current Knowledge ◽  
Research Field ◽  
New Drugs ◽  
Host Immune System ◽  
Immune Recognition ◽  
Genetic Associations ◽  
Efficient Treatment ◽  
Adaptive Immune

Since the identification of HIV and HCV much progress has been made in the understanding of their life cycle and interaction with the host immune system. Despite these viruses markedly differ in their virological properties and in their pathogenesis, they share many common features in their immune escape and survival strategy. Both viruses have developed sophisticated ways to subvert and antagonize host innate and adaptive immune responses. In the last years, much effort has been done in the study of the AIDS pathogenesis and in the development of efficient treatment strategies, and a fatal infection has been transformed in a potentially chronic pathology. Much of this knowledge is now being transferred in the HCV research field, especially in the development of new drugs, although a big difference still remains between the outcome of the two infections, being HCV eradicable after treatment, whereas HIV eradication remains at present unachievable due to the establishment of reservoirs. In this review, we present current knowledge on innate and adaptive immune recognition and activation during HIV and HCV mono-infections and evasion strategies. We also discuss the genetic associations between components of the immune system, the course of infection, and the outcome of the therapies.

scholarly journals WISP2 promotes cell proliferation via targeting ERK and YAP in ovarian cancer cells

2020 ◽  
Author(s):  
Zi-Qing Shi ◽  
Zi-Yan Chen ◽  
Yao Han ◽  
Heng-Yan Zhu ◽  
Meng-Dan Lyu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Inhibitory Effect ◽  
Ovarian Cancer Cells ◽  
Extracellular Signal ◽  
And Migration

Abstract Background: Wnt-inducible signaling pathway protein 2 (WISP2) is a wnt1-induced signaling pathway protein 2. Although studies indicate that WISP2 may promote the development of various tumors, its role in ovarian cancer remains unclear. The objective of the current study was to analyze the effects of WISP2 on the proliferation and migration of ovarian cancer cells in vitro and in vivo.Results: Immunohistochemistry and western blotting indicated that WISP2 was highly expressed in various ovarian cancer tissues and cell lines，but weakly expressed in normal ovary tissue. WISP2 deletion inhibited cell growth, clone formation, and migration of ovarian cancer cells while promoting cell apoptosis and affecting the cell cycle. This growth inhibitory effect caused by WISP2 loss is due to the inhibition of phosphorylated extracellular signal-related kinase (p-ERK)1/2, as well as CCAAT/enhancer-binding protein α (CEBPα) and CEPBβ. In addition, WISP2 deletion also activated the Yes-associated protein (YAP).Conclusion: WISP2 deletion inhibits ovarian cancer cell proliferation by affecting ERK signaling pathways.

scholarly journals Triptolide-Assisted Phosphorylation of p53 Suppresses Inflammation-Induced NF-κB Survival Pathways in Cancer Cells

2017 ◽  
Vol 37 (15) ◽  
Author(s):  
Li Zheng ◽  
Jia Jia ◽  
Huifang Dai ◽  
Lei Wan ◽  
Jian Liu ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Chronic Inflammation ◽  
Nuclear Translocation ◽  
Inhibitory Effects ◽  
Inflammatory Conditions ◽  
Survival Pathways ◽  
Extracellular Signal ◽  
Inflammatory Drugs ◽  
Iκbα Phosphorylation ◽  
Dependent Mechanism

ABSTRACT Chronic inflammation plays important roles in cancer initiation and progression. Resolving chronic inflammation or blocking inflammatory signal transduction may prevent cancer development. Here, we report that the combined low-dose use of two anti-inflammatory drugs, aspirin and triptolide, reduces spontaneous lung cancer incidence from 70% to 10% in a mouse model. Subsequent studies reveal that such treatment has little effect on resolving chronic inflammatory conditions in the lung, but it significantly blocks the NF-κB-mediated expression of proliferation and survival genes in cancer cells. Furthermore, triptolide and aspirin induce distinct mechanisms to potentiate each other to block NF-κB nuclear localization stimulated by inflammatory cytokines. While aspirin directly inhibits IκB kinases (IKKs) to phosphorylate IκBα for NF-κB activation, triptolide does not directly target IKKs or other factors that mediate IKK activation. Instead, it requires p53 to inhibit IκBα phosphorylation and degradation. Triptolide binds to and activates p38α and extracellular signal-regulated kinase 1/2 (ERK1/2), which phosphorylate and stabilize p53. Subsequently, p53 competes with IκBα for substrate binding to IKKβ and thereby blocks IκBα phosphorylation and NF-κB nuclear translocation. Inhibition of p38α and ERK1/2 or p53 mutations could abolish the inhibitory effects of triptolide on NF-κB. Our study defines a new p53-dependent mechanism for blocking NF-κB survival pathways in cancer cells.

scholarly journals Tools and Drugs for Purine-Binding Targets—Important Players in Inflammation and Cancer

Proceedings ◽  
2019 ◽  
Vol 22 (1) ◽  
pp. 33
Author(s):  
Christa E. Müller
Keyword(s):  
Immune System ◽  
Cancer Cells ◽  
Immune Escape ◽  
Gold Rush ◽  
Innate Immune ◽  
Receptor Subtypes ◽  
Cancer Cell Proliferation ◽  
A2b Receptor ◽  
Cancer Tissues ◽  
Adenosine A2a

Despite decades of research, only few drugs have been approved that interact with purine receptors. Recently, new hypes and hopes have been created in the field, mainly due to the gold rush fever in immuno-oncology. Adenosine is one of the strongest immunosuppressant agents of the innate immune system. Cancer cells and tissues can release large amounts of ATP, which is immediately hydrolyzed by ectonucleotidases. These ecto-enzymes, including ectonucleotide pyrophosphatase/phosphodiesterase 1 (NPP1, CD203a), ectonucleoside diphospho­hydrolase 1 (NTPDase1, CD39), and ecto-5′-nucleotidase (CD73), are upregulated on many cancer cells, leading to the production of adenosine. The cloud of adenosine formed around cancer tissues contributes to immune escape by interacting with adenosine A2A and A2B receptor subtypes (A2AAR, A2BAR) on immune cells. In addition, activation of A2BARs by adenosine enhances cancer cell proliferation, metastasis, and angiogenesis. Blockade of A2A and A2B adenosine receptors and/or inhibition of adenosine formation by blocking ectonucleotidases are being pursued as novel principles that activate the immune system to defeat cancer. Recent progress in the development of adenosine receptor antagonists and ectonucleotidase inhibitors will be presented and discussed.

scholarly journals Immunology and Immunotherapy of Head and Neck Cancer

2015 ◽  
Vol 33 (29) ◽  
pp. 3293-3304 ◽  
Author(s):  
Robert L. Ferris
Keyword(s):  
Squamous Cell Carcinoma ◽  
Head And Neck Cancer ◽  
Immune System ◽  
Head And Neck ◽  
Neck Cancer ◽  
Immune Escape ◽  
Cell Types ◽  
Host Immune System ◽  
Infiltrating Cells ◽  
Cancer Immunosurveillance

The immune system plays a key role in the development, establishment, and progression of head and neck squamous cell carcinoma (HNSCC). A greater understanding of the dysregulation and evasion of the immune system in the evolution and progression of HNSCC provides the basis for improved therapies and outcomes for patients. HNSCC cells evade the host immune system through manipulation of their own immunogenicity, production of immunosuppressive mediators, and promotion of immunomodulatory cell types. Through the tumor's influence on the microenvironment, the immune system can be exploited to promote metastasis, angiogenesis, and growth. This article provides a brief overview of key components of the immune infiltrating cells in the tumor microenvironment, reviewing immunological principles related to head and neck cancer, including the concept of cancer immunosurveillance and immune escape. Current immunotherapeutic strategies and emerging results from ongoing clinical trials are presented.

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