Immunometabolism in bladder cancer microenvironment

2022 ◽  
Vol 22 ◽  
Author(s):  
Mohammad Javad Fattahi ◽  
Mohammad Reza Haghshenas ◽  
Abbas Ghaderi
Keyword(s):  
Bladder Cancer ◽  
Immune Cells ◽  
Cell Function ◽  
Immune Cell ◽  
Metabolic Reprogramming ◽  
Immune Cell Function ◽  
Complex Interactions ◽  
Metabolite Accumulation ◽  
And Migration

Abstract: The initiation and progression of bladder cancer (BC), is dependent on its tumor microenvironment (TME). On the other hand, cancer cells shape and train TME to support their development, respond to treatment and migration in an organism. Immune cells exert key roles in the BC microenvironment and have complex interactions with BC cells. These complicated interplays result in metabolic competition in the TME leading to nutrient deprivation, acidosis, hypoxia and metabolite accumulation, which impair immune cell function. Recent studies have demonstrated that immune cells functions are closely correlated with their metabolism. Immunometabolism describes the functional metabolic alterations that take place within immune cells and the role of these cells in directing metabolism and immune response in tissues or diseases such as cancer. Some molecules and their metabolites in the TME including glucose, fatty acids and amino acids can regulate the phenotype, function and metabolism of immune cells. Hence, here we describe some recent advances in immunometabolism and relate them to BC progression. A profound understanding of the metabolic reprogramming of BC cells and immune cells in the TME will offer novel opportunities for targeted therapies in future.

scholarly journals STAT3, a Master Regulator of Anti-Tumor Immune Response

Cancers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1280 ◽  
Author(s):  
Rébé ◽  
Ghiringhelli
Keyword(s):  
Cancer Progression ◽  
Immune Cells ◽  
Cell Function ◽  
Immune Cell ◽  
Checkpoint Inhibitors ◽  
Cancer Growth ◽  
Signal Transducer ◽  
Immune Cell Function ◽  
Transcription 3

Immune cells in the tumor microenvironment regulate cancer growth. Thus cancer progression is dependent on the activation or repression of transcription programs involved in the proliferation/activation of lymphoid and myeloid cells. One of the main transcription factors involved in many of these pathways is the signal transducer and activator of transcription 3 (STAT3). In this review we will focus on the role of STAT3 and its regulation, e.g. by phosphorylation or acetylation in immune cells and how it might impact immune cell function and tumor progression. Moreover, we will review the ability of STAT3 to regulate checkpoint inhibitors.

scholarly journals Adaptive immunity at the crossroads of autophagy and metabolism

2021 ◽  
Author(s):  
Shree Padma Metur ◽  
Daniel J. Klionsky
Keyword(s):  
Immune Cells ◽  
Cell Function ◽  
Immune Cell ◽  
Metabolic Stress ◽  
Energy Availability ◽  
Immune Cell Function ◽  
Adaptive Immune ◽  
Adaptive Immune Cells ◽  
Protein Synthesis Machinery

AbstractThe function of lymphocytes is dependent on their plasticity, particularly their adaptation to energy availability and environmental stress, and their protein synthesis machinery. Lymphocytes are constantly under metabolic stress, and macroautophagy/autophagy is the primary metabolic pathway that helps cells overcome stressors. The intrinsic role of autophagy in regulating the metabolism of adaptive immune cells has recently gained increasing attention. In this review, we summarize and discuss the versatile roles of autophagy in regulating cellular metabolism and the implications of autophagy for immune cell function and fate, especially for T and B lymphocytes.

scholarly journals Altered Ca2+ Homeostasis in Immune Cells during Aging: Role of Ion Channels

2020 ◽  
Vol 22 (1) ◽  
pp. 110
Author(s):  
Dorina Zöphel ◽  
Chantal Hof ◽  
Annette Lis
Keyword(s):  
Immune Cells ◽  
Irreversible Process ◽  
Cell Function ◽  
Immune Cell ◽  
Compensatory Mechanisms ◽  
Cellular Environment ◽  
Age Related ◽  
Dependent Processes ◽  
Equal Density

Aging is an unstoppable process and begins shortly after birth. Each cell of the organism is affected by the irreversible process, not only with equal density but also at varying ages and with different speed. Therefore, aging can also be understood as an adaptation to a continually changing cellular environment. One of these very prominent changes in age affects Ca2+ signaling. Especially immune cells highly rely on Ca2+-dependent processes and a strictly regulated Ca2+ homeostasis. The intricate patterns of impaired immune cell function may represent a deficit or compensatory mechanisms. Besides, altered immune function through Ca2+ signaling can profoundly affect the development of age-related disease. This review attempts to summarize changes in Ca2+ signaling due to channels and receptors in T cells and beyond in the context of aging.

scholarly journals Identification of a prostaglandin E2 receptor that regulates mosquito oenocytoid immune cell function in limiting bacteria and parasite infection

2020 ◽  
Author(s):  
Hyeogsun Kwon ◽  
David R. Hall ◽  
Ryan C. Smith
Keyword(s):  
Immune Responses ◽  
Prostaglandin E2 ◽  
Cell Function ◽  
Immune Cell ◽  
Protective Effects ◽  
Immune Cell Function ◽  
Humoral Immune ◽  
High Concentrations ◽  
Prostaglandin E2 Receptor

AbstractLipid-derived signaling molecules known as eicosanoids have integral roles in mediating immune and inflammatory processes across metazoans. This includes the function of prostaglandins and their cognate G protein-coupled receptors (GPCRs) to employ their immunological actions. In insects, prostaglandins have been implicated in the regulation of both cellular and humoral immune responses, yet studies have been limited by the absence of a described prostaglandin receptor. Here, we characterize a prostaglandin E2 receptor (AgPGE2R) in the mosquito Anopheles gambiae and examine its contributions to innate immunity. AgPGE2R expression is most abundant in circulating hemocytes where it is primarily localized to oenocytoid immune cell populations. Through the administration of prostaglandin E2 (PGE2) and AgPGE2R-silencing by RNAi, we demonstrate that PGE2 signaling regulates the expression of a subset of prophenoloxidases (PPOs) and antimicrobial peptides (AMPs). PGE2 priming via the AgPGE2R significantly limited bacterial replication and suppressed Plasmodium oocyst survival. Additional experiments establish that PGE2 priming increases phenoloxidase (PO) activity through the increased expression of PPO1 and PPO3, which significantly influence Plasmodium oocyst survival. We also provide evidence that PGE2 priming is concentration-dependent, where high concentrations of PGE2 promote oenocytoid lysis, negating the protective effects of PGE2 priming on anti-Plasmodium immunity. Taken together, our results characterize the AgPGE2R and the role of prostaglandin signaling on immune cell function, providing new insights into the role of PGE2 on anti-bacterial and anti-Plasmodium immune responses in the mosquito host.

scholarly journals Thyroid hormone metabolism in innate immune cells

2017 ◽  
Vol 232 (2) ◽  
pp. R67-R81 ◽  
Author(s):  
Anne H van der Spek ◽  
Eric Fliers ◽  
Anita Boelen
Keyword(s):  
Thyroid Hormone ◽  
Immune Cells ◽  
Cellular Response ◽  
Cell Function ◽  
Immune Cell ◽  
Innate Immune ◽  
Innate Immune Cell ◽  
Extensive Literature ◽  
Innate Immune Cells ◽  
Immune Cell Function

Thyroid hormone (TH) metabolism and thyroid status have been linked to various aspects of the immune response. There is extensive literature available on the effects of thyroid hormone on innate immune cells. However, only recently have authors begun to study the mechanisms behind these effects and the role of intracellular TH metabolism in innate immune cell function during inflammation. This review provides an overview of the molecular machinery of intracellular TH metabolism present in neutrophils, macrophages and dendritic cells and the role and effects of intracellular TH metabolism in these cells. Circulating TH levels have a profound effect on neutrophil, macrophage and dendritic cell function. In general, increased TH levels result in an amplification of the pro-inflammatory response of these cells. The mechanisms behind these effects include both genomic and non-genomic effects of TH. Besides a pro-inflammatory effect induced by extracellular TH, the cellular response to pro-inflammatory stimuli appears to be dependent on functional intracellular TH metabolism. This is illustrated by the fact that the deiodinase enzymes and in some cell types also thyroid hormone receptors appear to be crucial for adequate innate immune cell function. This overview of the literature suggests that TH metabolism plays an important role in the host defence against infection through the modulation of innate immune cell function.

Thyroid Hormone and Deiodination in Innate Immune Cells

Endocrinology ◽  
2020 ◽  
Vol 162 (1) ◽  
Author(s):  
Anne H van der Spek ◽  
Eric Fliers ◽  
Anita Boelen
Keyword(s):  
Thyroid Hormone ◽  
Immune Cells ◽  
Cell Function ◽  
Immune Cell ◽  
Innate Immune ◽  
Innate Immune Cell ◽  
Innate Immune Cells ◽  
Immune Cell Function ◽  
Hormone Metabolism ◽  
Thyroid Hormone Metabolism

Abstract Thyroid hormone has recently been recognized as an important determinant of innate immune cell function. Highly specialized cells of the innate immune system, including neutrophils, monocytes/macrophages, and dendritic cells, are capable of identifying pathogens and initiating an inflammatory response. They can either phagocytose and kill microbes, or recruit other innate or adaptive immune cells to the site of inflammation. Innate immune cells derive from the hematopoietic lineage and are generated in the bone marrow, from where they can be recruited into the blood and tissues in the case of infection. The link between the immune and endocrine systems is increasingly well established, and recent studies have shown that innate immune cells can be seen as important thyroid hormone target cells. Tight regulation of cellular thyroid hormone availability and action is performed by thyroid hormone transporters, receptors, and the deiodinase enzymes. Innate immune cells express all these molecular elements of intracellular thyroid hormone metabolism. Interestingly, there is recent evidence for a causal relationship between cellular thyroid hormone status and innate immune cell function. This review describes the effects of modulation of intracellular thyroid hormone metabolism on innate immune cell function, specifically neutrophils, macrophages, and dendritic cells, with a special focus on the deiodinase enzymes. Although there are insufficient data at this stage for conclusions on the clinical relevance of these findings, thyroid hormone metabolism may partially determine the innate immune response and, by inference, the clinical susceptibility to infections.

The role of sodium in modulating immune cell function

2019 ◽  
Vol 15 (9) ◽  
pp. 546-558 ◽  
Author(s):  
Nicola Wilck ◽  
András Balogh ◽  
Lajos Markó ◽  
Hendrik Bartolomaeus ◽  
Dominik N. Müller
Keyword(s):  
Cell Function ◽  
Immune Cell ◽  
Immune Cell Function

scholarly journals Small molecule AZD4635 inhibitor of A2AR signaling rescues immune cell function including CD103+ dendritic cells enhancing anti-tumor immunity

2020 ◽  
Vol 8 (2) ◽  
pp. e000417 ◽  
Author(s):  
Alexandra Borodovsky ◽  
Christine M Barbon ◽  
Yanjun Wang ◽  
Minwei Ye ◽  
Laura Prickett ◽  
...  
Keyword(s):  
T Cell ◽  
Antigen Presentation ◽  
Small Molecule ◽  
Immune Cells ◽  
Antitumor Immunity ◽  
Cell Function ◽  
Immune Cell ◽  
T Cell Function ◽  
Adenosine Signaling

Accumulation of extracellular adenosine within the microenvironment is a strategy exploited by tumors to escape detection by the immune system. Adenosine signaling through the adenosine 2A receptor (A2AR) on immune cells elicits a range of immunosuppressive effects which promote tumor growth and limit the efficacy of immune checkpoint inhibitors. Preclinical data with A2AR inhibitors have demonstrated tumor regressions in mouse models by rescuing T cell function; however, the mechanism and role on other immune cells has not been fully elucidated.MethodsWe report here the development of a small molecule A2AR inhibitor including characterization of binding and inhibition of A2AR function with varying amounts of a stable version of adenosine. Functional activity was tested in both mouse and human T cells and dendritic cells (DCs) in in vitro assays to understand the intrinsic role on each cell type. The role of adenosine and A2AR inhibition was tested in DC differentiation assays as well as co-culture assays to access the cross-priming function of DCs. Syngeneic models were used to assess tumor growth alone and in combination with alphaprogrammed death-ligand 1 (αPD-L1). Immunophenotyping by flow cytometry was performed to examine global immune cell changes upon A2AR inhibition.ResultsWe provide the first report of AZD4635, a novel small molecule A2AR antagonist which inhibits downstream signaling and increases T cell function as well as a novel mechanism of enhancing antigen presentation by CD103+ DCs. The role of antigen presentation by DCs, particularly CD103+ DCs, is critical to drive antitumor immunity providing rational to combine a priming agent AZD4635 with check point blockade. We find adenosine impairs the maturation and antigen presentation function of CD103+ DCs. We show in multiple syngeneic mouse tumor models that treatment of AZD4635 alone and in combination with αPD-L1 led to decreased tumor volume correlating with enhanced CD103+ function and T cell response. We extend these studies into human DCs to show that adenosine promotes a tolerogenic phenotype that can be reversed with AZD4635 restoring antigen-specific T cell activation. Our results support the novel role of adenosine signaling as an intrinsic negative regulator of CD103+ DCs maturation and priming. We show that potent inhibition of A2AR with AZD4635 reduces tumor burden and enhances antitumor immunity. This unique mechanism of action in CD103+ DCs may contribute to clinical responses as AZD4635 is being evaluated in clinical trials with IMFINZI (durvalumab, αPD-L1) in patients with solid malignancies.ConclusionWe provide evidence implicating suppression of adaptive and innate immunity by adenosine as a mechanism for immune evasion by tumors. Inhibition of adenosine signaling through selective small molecule inhibition of A2AR using AZD4635 restores T cell function via an internal mechanism as well as tumor antigen cross-presentation by CD103+ DCs resulting in antitumor immunity.

scholarly journals LRRK2 regulation of immune-pathways and inflammatory disease

2019 ◽  
Vol 47 (6) ◽  
pp. 1581-1595 ◽  
Author(s):  
Rebecca L. Wallings ◽  
Malú G. Tansey
Keyword(s):  
Immune Cells ◽  
Cell Function ◽  
Immune Cell ◽  
Cell Types ◽  
Rab Gtpases ◽  
Sporadic Cases ◽  
Bona Fide ◽  
Pathway Regulation ◽  
Different Cell Types

Mutations in the leucine-rich-repeat kinase 2 (LRRK2) gene are associated with familial and sporadic cases of Parkinson's disease but are also found in immune-related disorders such as inflammatory bowel disease, tuberculosis and leprosy. LRRK2 is highly expressed in immune cells and has been functionally linked to pathways pertinent to immune cell function, such as cytokine release, autophagy and phagocytosis. Here, we examine the current understanding of the role of LRRK2 kinase activity in pathway regulation in immune cells, drawing upon data from multiple diseases associated with LRRK2 to highlight the pleiotropic effects of LRRK2 in different cell types. We discuss the role of the bona fide LRRK2 substrate, Rab GTPases, in LRRK2 pathway regulation as well as downstream events in the autophagy and inflammatory pathways.

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