scholarly journals Hypoxia-Driven Immune Escape in the Tumor Microenvironment

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 992 ◽  
Author(s):  
Alyssa Vito ◽  
Nader El-Sayes ◽  
Karen Mossman
Keyword(s):  
Cell Death ◽  
Tumor Microenvironment ◽  
Immune Escape ◽  
Cell Types ◽  
Cell Death Pathways ◽  
Hypoxic Conditions ◽  
Complex Ecosystem ◽  
Different Cell Types ◽  
Immune Detection ◽  
Immunosuppressive Cytokines

The tumor microenvironment is a complex ecosystem comprised of many different cell types, abnormal vasculature and immunosuppressive cytokines. The irregular growth kinetics with which tumors grow leads to increased oxygen consumption and, in turn, hypoxic conditions. Hypoxia has been associated with poor clinical outcome, increased tumor heterogeneity, emergence of resistant clones and evasion of immune detection. Additionally, hypoxia-driven cell death pathways have traditionally been thought of as tolerogenic processes. However, as researchers working in the field of immunotherapy continue to investigate and unveil new types of immunogenic cell death (ICD), it has become clear that, in some instances, hypoxia may actually induce ICD within a tumor. In this review, we will discuss hypoxia-driven immune escape that drives poor prognostic outcomes, the ability of hypoxia to induce ICD and potential therapeutic targets amongst hypoxia pathways.

scholarly journals Distinct and Atypical Intrinsic and Extrinsic Cell Death Pathways between Photoreceptor Cell Types upon Specific Ablation of Ranbp2 in Cone Photoreceptors

PLoS Genetics ◽  
2013 ◽  
Vol 9 (6) ◽  
pp. e1003555 ◽  
Author(s):  
Kyoung-in Cho ◽  
MdEmdadul Haque ◽  
Jessica Wang ◽  
Minzhong Yu ◽  
Ying Hao ◽  
...  
Keyword(s):  
Cell Death ◽  
Photoreceptor Cell ◽  
Cell Types ◽  
Cone Photoreceptors ◽  
Cell Death Pathways

scholarly journals The Influence of Tumor Microenvironment on Immune Escape of Melanoma

2020 ◽  
Vol 21 (21) ◽  
pp. 8359 ◽  
Author(s):  
Aleksandra Simiczyjew ◽  
Ewelina Dratkiewicz ◽  
Justyna Mazurkiewicz ◽  
Marcin Ziętek ◽  
Rafał Matkowski ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Immune Escape ◽  
Cell Types ◽  
Melanoma Cells ◽  
Cancer Therapies ◽  
System A ◽  
Anti Cancer ◽  
Low Efficiency ◽  
Inflammatory Molecules

The low efficiency of currently-used anti-cancer therapies poses a serious challenge, especially in the case of malignant melanoma, a cancer characterized by elevated invasiveness and relatively high mortality rate. The role of the tumor microenvironment in the progression of melanoma and its acquisition of resistance to treatment seems to be the main focus of recent studies. One of the factors that, in normal conditions, aids the organism in its fight against the cancer and, following the malignant transformation, adapts to facilitate the development of the tumor is the immune system. A variety of cell types, i.e., T and B lymphocytes, macrophages, and dendritic and natural killer cells, as well as neutrophils, support the growth and invasiveness of melanoma cells, utilizing a plethora of mechanisms, including secretion of pro-inflammatory molecules, induction of inhibitory receptors expression, or depletion of essential nutrients. This review provides a comprehensive summary of the processes regulated by tumor-associated cells that promote the immune escape of melanoma cells. The described mechanisms offer potential new targets for anti-cancer treatment and should be further studied to improve currently-employed therapies.

Presenilin-interacting proteins

2002 ◽  
Vol 4 (19) ◽  
pp. 1-18 ◽  
Author(s):  
Qi Chen ◽  
David Schubert
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Death ◽  
Cell Types ◽  
Cellular Adhesion ◽  
Interacting Proteins ◽  
Missense Mutations ◽  
Cell Death Pathways ◽  
Physiological Relevance ◽  
Genes Encoding

Familial Alzheimer's disease (FAD) accounts for 5–10% of deaths from Alzheimer's disease (AD), and approximately 50% of these cases have been definitely linked to missense mutations in three genes, encoding the amyloid precursor protein (APP), presenilin 1 (PS1) and presenilin 2 (PS2). Of these, the vast majority of FAD-linked mutations are within PS1. There has been an extensive effort to identify proteins that functionally interact with PS1 and PS2 because of their clear roles in FAD. The goal of this review is to describe these proteins and to discuss in more detail the probable biological functions of a subset of the better-studied interacting proteins. In particular, the review examines APP, Notch, nicastrin, modifier of cellular adhesion (MOCA), β-catenin, and the group of proteins involved in cell death, calcium metabolism and cell adhesion. We argue that, although a few of the interacting proteins are unambiguously involved in well-studied cellular pathways, their exact roles within these pathways have not been clearly defined, and indeed might vary between cell types. We also question the physiological relevance of some of the work linking PS to cell death pathways. Finally, we point out the value of using flies and worms to sort out the often contradictory work in the PS field, and we mention how knowledge of PS-interacting pathways will contribute to the development of new therapeutic strategies in AD.

scholarly journals Tumor Microenvironment-Derived Metabolites: A Guide to Find New Metabolic Therapeutic Targets and Biomarkers

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3230
Author(s):  
Juan C. García-Cañaveras ◽  
Agustín Lahoz
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Cancer Metabolism ◽  
Immune Escape ◽  
Positron Emission Tomography Imaging ◽  
Therapy Response ◽  
Cell Types ◽  
Metabolic Reprogramming ◽  
Positron Emission ◽  
Efficient Delivery

Metabolic reprogramming is a hallmark of cancer that enables cancer cells to grow, proliferate and survive. This metabolic rewiring is intrinsically regulated by mutations in oncogenes and tumor suppressors, but also extrinsically by tumor microenvironment factors (nutrient and oxygen availability, cell-to-cell interactions, cytokines, hormones, etc.). Intriguingly, only a few cancers are driven by mutations in metabolic genes, which lead metabolites with oncogenic properties (i.e., oncometabolites) to accumulate. In the last decade, there has been rekindled interest in understanding how dysregulated metabolism and its crosstalk with various cell types in the tumor microenvironment not only sustains biosynthesis and energy production for cancer cells, but also contributes to immune escape. An assessment of dysregulated intratumor metabolism has long since been exploited for cancer diagnosis, monitoring and therapy, as exemplified by 18F-2-deoxyglucose positron emission tomography imaging. However, the efficient delivery of precision medicine demands less invasive, cheaper and faster technologies to precisely predict and monitor therapy response. The metabolomic analysis of tumor and/or microenvironment-derived metabolites in readily accessible biological samples is likely to play an important role in this sense. Here, we review altered cancer metabolism and its crosstalk with the tumor microenvironment to focus on energy and biomass sources, oncometabolites and the production of immunosuppressive metabolites. We provide an overview of current pharmacological approaches targeting such dysregulated metabolic landscapes and noninvasive approaches to characterize cancer metabolism for diagnosis, therapy and efficacy assessment.

scholarly journals Iron Overload, Oxidative Stress, and Ferroptosis in the Failing Heart and Liver

Antioxidants ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1864
Author(s):  
Daniele Mancardi ◽  
Mariarosa Mezzanotte ◽  
Elisa Arrigo ◽  
Alice Barinotti ◽  
Antonella Roetto
Keyword(s):  
Cell Death ◽  
Iron Overload ◽  
Redox Homeostasis ◽  
Cell Types ◽  
Iron Accumulation ◽  
Oxygen Species ◽  
Hepatic Inflammation ◽  
Mitochondrial Structure ◽  
Different Cell Types

Iron accumulation is a key mediator of several cytotoxic mechanisms leading to the impairment of redox homeostasis and cellular death. Iron overload is often associated with haematological diseases which require regular blood transfusion/phlebotomy, and it represents a common complication in thalassaemic patients. Major damages predominantly occur in the liver and the heart, leading to a specific form of cell death recently named ferroptosis. Different from apoptosis, necrosis, and autophagy, ferroptosis is strictly dependent on iron and reactive oxygen species, with a dysregulation of mitochondrial structure/function. Susceptibility to ferroptosis is dependent on intracellular antioxidant capacity and varies according to the different cell types. Chemotherapy-induced cardiotoxicity has been proven to be mediated predominantly by iron accumulation and ferroptosis, whereas there is evidence about the role of ferritin in protecting cardiomyocytes from ferroptosis and consequent heart failure. Another paradigmatic organ for transfusion-associated complication due to iron overload is the liver, in which the role of ferroptosis is yet to be elucidated. Some studies report a role of ferroptosis in the initiation of hepatic inflammation processes while others provide evidence about an involvement in several pathologies including immune-related hepatitis and acute liver failure. In this manuscript, we aim to review the literature to address putative common features between the response to ferroptosis in the heart and liver. A better comprehension of (dys)similarities is pivotal for the development of future therapeutic strategies that can be designed to specifically target this type of cell death in an attempt to minimize iron-overload effects in specific organs.

scholarly journals PANoptosis: A New Insight Into Oral Infectious Diseases

2021 ◽  
Vol 12 ◽  
Author(s):  
Weiyi Jiang ◽  
Zilong Deng ◽  
Xingzhu Dai ◽  
Wanghong Zhao
Keyword(s):  
Cell Death ◽  
Infectious Diseases ◽  
Classical Model ◽  
Cell Types ◽  
Oral Microbiome ◽  
Host Cells ◽  
Tissue Destruction ◽  
Death Studies ◽  
Cell Death Pathways ◽  
Single Term

The oral microbiome, one of the most complex and intensive microbial ecosystems in the human body, comprises bacteria, archaea, fungi, protozoa, and viruses. Dysbiosis of the oral microbiome is the initiating factor that leads to oral infectious diseases. Infection is a sophisticated biological process involving interplay between the pathogen and the host, which often leads to activation of programmed cell death. Studies suggest that pyroptosis, apoptosis, and necroptosis are involved in multiple oral infectious diseases. Further understanding of crosstalk between cell death pathways has led to pyroptosis, apoptosis, and necroptosis being integrated into a single term: PANoptosis. PANoptosis is a multifaceted agent of the immune response that has important pathophysiological relevance to infectious diseases, autoimmunity, and cancer. As such, it plays an important role in innate immune cells that detect and eliminate intracellular pathogens. In addition to the classical model of influenza virus-infected and Yersinia-infected macrophages, other studies have expanded the scope of PANoptosis to include other microorganisms, as well as potential roles in cell types other than macrophages. In this review, we will summarize the pathophysiological mechanisms underlying inflammation and tissue destruction caused by oral pathogens. We present an overview of different pathogens that may induce activation of PANoptosis, along with the functional consequences of PANoptosis in the context of oral infectious diseases. To advance our understanding of immunology, we also explore the strategies used by microbes that enable immune evasion and replication within host cells. Improved understanding of the interplay between the host and pathogen through PANoptosis will direct development of therapeutic strategies that target oral infectious diseases.

scholarly journals Metabolism in the Tumor Microenvironment

2020 ◽  
Vol 4 (1) ◽  
pp. 17-40 ◽  
Author(s):  
Allison N. Lau ◽  
Matthew G. Vander Heiden
Keyword(s):  
Endothelial Cells ◽  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Metabolic Pathways ◽  
Stromal Cell ◽  
Cancer Metabolism ◽  
Cell Types ◽  
Cell Type ◽  
Therapeutic Targeting ◽  
Different Cell Types

Experiments in culture systems where one cell type is provided with abundant nutrients and oxygen have been used to inform much of our understanding of cancer metabolism. However, many differences have been observed between the metabolism of tumors and the metabolism of cancer cells grown in monoculture. These differences reflect, at least in part, the presence of nonmalignant cells in the tumor microenvironment and the interactions between those cells and cancer cells. However, less is known about how the metabolism of various tumor stromal cell types differs from that of cancer cells, and how this difference might inform therapeutic targeting of metabolic pathways. Emerging data have identified both cooperative and competitive relationships between different cell types in a tumor, and this review examines how four abundant stromal cell types in the tumor microenvironment, fibroblasts, T cells, macrophages, and endothelial cells, contribute to the metabolism of tumors.

scholarly journals Time-resolved characterization of the mechanisms of toxicity induced by silica and amino-modified polystyrene on alveolar-like macrophages

2019 ◽  
Vol 94 (1) ◽  
pp. 173-186 ◽  
Author(s):  
Sarah Deville ◽  
Birgit Honrath ◽  
Quynh T. D. Tran ◽  
Gyorgy Fejer ◽  
Ivo Lambrichts ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Types ◽  
Similar Time ◽  
Time Resolved ◽  
Membrane Hyperpolarization ◽  
Mechanisms Of Toxicity ◽  
Cellular Reactive Oxygen Species ◽  
Foreign Materials ◽  
Modified Polystyrene ◽  
Different Cell Types

Abstract Macrophages play a major role in the removal of foreign materials, including nano-sized materials, such as nanomedicines and other nanoparticles, which they accumulate very efficiently. Because of this, it is recognized that for a safe development of nanotechnologies and nanomedicine, it is essential to investigate potential effects induced by nano-sized materials on macrophages. To this aim, in this work, a recently established model of primary murine alveolar-like macrophages was used to investigate macrophage responses to two well-known nanoparticle models: 50 nm amino-modified polystyrene, known to induce cell death via lysosomal damage and apoptosis in different cell types, and 50 nm silica nanoparticles, which are generally considered non-toxic. Then, a time-resolved study was performed to characterize in detail the response of the macrophages following exposure to the two nanoparticles. As expected, exposure to the amino-modified polystyrene led to cell death, but surprisingly no lysosomal swelling or apoptosis were detected. On the contrary, a peculiar mitochondrial membrane hyperpolarization was observed, accompanied by endoplasmic reticulum stress (ER stress), increased cellular reactive oxygen species (ROS) and changes of metabolic activity, ultimately leading to cell death. Strong toxic responses were observed also after exposure to silica, which included mitochondrial ROS production, mitochondrial depolarization and cell death by apoptosis. Overall, these results showed that exposure to the two nanoparticles led to a very different series of intracellular events, suggesting that the macrophages responded differently to the two nanoparticle models. Similar time-resolved studies are required to characterize the response of macrophages to nanoparticles, as a key parameter in nanosafety assessment.

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