scholarly journals Shedding Light on the Role of Neurotransmitters in the Microenvironment of Pancreatic Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Yiyi Liang ◽  
Huimin Li ◽  
Yu Gan ◽  
Hong Tu
Keyword(s):  
Pancreatic Cancer ◽  
Immune Responses ◽  
Cancer Cells ◽  
Immune Cells ◽  
Stromal Cells ◽  
Biological Behavior ◽  
Adaptive Immune ◽  
Extracellular Matrix Components ◽  
Cellular Components

Pancreatic cancer (PC) is a highly lethal malignancy with a 5-year survival rate of less than 8%. The fate of PC is determined not only by the malignant behavior of the cancer cells, but also by the surrounding tumor microenvironment (TME), consisting of various cellular (cancer cells, immune cells, stromal cells, endothelial cells, and neurons) and non-cellular (cytokines, neurotransmitters, and extracellular matrix) components. The pancreatic TME has the unique characteristic of exhibiting increased neural density and altered microenvironmental concentration of neurotransmitters. The neurotransmitters, produced by both neuron and non-neuronal cells, can directly regulate the biological behavior of PC cells via binding to their corresponding receptors on tumor cells and activating the intracellular downstream signals. On the other hand, the neurotransmitters can also communicate with other cellular components such as the immune cells in the TME to promote cancer growth. In this review, we will summarize the pleiotropic effects of neurotransmitters on the initiation and progression of PC, and particularly discuss the emerging mechanisms of how neurotransmitters influence the innate and adaptive immune responses in the TME in an autocrine or paracrine manner. A better understanding of the interplay between neurotransmitters and the immune cells in the TME might facilitate the development of new effective therapies for PC.

scholarly journals Role of Histamine in Modulating the Immune Response and Inflammation

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Anna Cláudia Calvielli Castelo Branco ◽  
Fábio Seiti Yamada Yoshikawa ◽  
Anna Julia Pietrobon ◽  
Maria Notomi Sato
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Immune Cells ◽  
Inflammatory Mediators ◽  
Pleiotropic Effect ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Regulatory Functions ◽  
Proinflammatory Factors

Inflammatory mediators, including cytokines, histamine, bradykinin, prostaglandins, and leukotrienes, impact the immune system, usually as proinflammatory factors. Other mediators act as regulatory components to establish homeostasis after injury or prevent the inflammatory process. Histamine, a biogenic vasoactive amine, causes symptoms such as allergies and has a pleiotropic effect that is dependent on its interaction with its four histamine receptors. In this review, we discuss the dualistic effects of histamine: how histamine affects inflammation of the immune system through the activation of intracellular pathways that induce the production of inflammatory mediators and cytokines in different immune cells and how histamine exerts regulatory functions in innate and adaptive immune responses. We also evaluate the interactions between these effects.

Role of Tumor Microenvironment in Cancer Stem Cells Resistance to Radiotherapy

2021 ◽  
Vol 22 ◽  
Author(s):  
Shahram Taeb ◽  
Milad Ashrafizadeh ◽  
Ali Zarrabi ◽  
Saeed Rezapoor ◽  
Ahmed Eleojo Musa ◽  
...  
Keyword(s):  
Stem Cells ◽  
Tumor Microenvironment ◽  
Cancer Stem Cells ◽  
Immune Responses ◽  
Immune Cells ◽  
Stromal Cells ◽  
Hypoxia Inducible Factor ◽  
Proliferation Capacity ◽  
Chronic Disorder

Abstract: Cancer is a chronic disorder that involves several elements of both the tumor and the host stromal cells. At present, the complex relationship between the various factors presents in the tumor microenvironment (TME) and tumor cells, as well as immune cells located within the TME, is still poorly known. Within the TME, the crosstalk of these factors and immune cells essentially determines how a tumor reacts to the treatment and how the tumor can ultimately be destroyed, remain dormant, or develop and metastasize. Also, in TME, reciprocal crosstalk between cancer-associated fibroblasts (CAFs), extracellular matrix (ECM), hypoxia-inducible factor (HIF) intensifies the proliferation capacity of cancer stem cells (CSCs). CSCs are subpopulation of cells that reside within the tumor bulk and have the capacity to self-renew, differentiate, and repair DNA damage. These characteristics make CSCs develop resistance to a variety of treatments, such as radiotherapy (RT). RT is a frequent and often curative treatment for local cancer which mediates tumor elimination by cytotoxic actions. Also, cytokines and growth factors that are released into TME, have been involved in the activation of tumor radioresistance and the induction of different immune cells, altering local immune responses. In this review, we discuss the pivotal role of TME in resistance of CSCs to RT.

scholarly journals The Role of Myeloid Cells in Acute Kidney Injury and Kidney Repair

Kidney360 ◽  
2021 ◽  
Vol 2 (11) ◽  
pp. 1852-1864
Author(s):  
Leyuan Xu
Keyword(s):  
Acute Kidney Injury ◽  
Immune Responses ◽  
Immune Cells ◽  
Experimental Studies ◽  
Myeloid Cells ◽  
Kidney Injury ◽  
Adaptive Immune Responses ◽  
Injury Repair ◽  
Adaptive Immune

AKI remains highly prevalent, yet no optimal therapy is available to prevent it or promote recovery after initial insult. Experimental studies have demonstrated that both innate and adaptive immune responses play a central role during AKI. In response to injury, myeloid cells are first recruited and activated on the basis of specific signals from the damaged microenvironment. The subsequent recruitment and activation state of the immune cells depends on the stage of injury and recovery, reflecting a dynamic and diverse spectrum of immunophenotypes. In this review, we highlight our current understanding of the mechanisms by which myeloid cells contribute to injury, repair, and fibrosis after AKI.

scholarly journals Triptolide targets super-enhancer networks in pancreatic cancer cells and cancer-associated fibroblasts

Oncogenesis ◽  
2020 ◽  
Vol 9 (11) ◽  
Author(s):  
Pawan Noel ◽  
Shaimaa Hussein ◽  
Serina Ng ◽  
Corina E. Antal ◽  
Wei Lin ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Antitumor Activity ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Stromal Cells ◽  
Cancer Associated Fibroblasts ◽  
Cell Type ◽  
Pancreatic Cancer Cells ◽  
Cell Type Specific

Abstract The tumor microenvironment in pancreatic ductal adenocarcinoma (PDAC) is highly heterogeneous, fibrotic, and hypovascular, marked by extensive desmoplasia and maintained by the tumor cells, cancer-associated fibroblasts (CAFs) and other stromal cells. There is an urgent need to identify and develop treatment strategies that not only target the tumor cells but can also modulate the stromal cells. A growing number of studies implicate the role of regulatory DNA elements called super-enhancers (SE) in maintaining cell-type-specific gene expression networks in both normal and cancer cells. Using chromatin activation marks, we first mapped SE networks in pancreatic CAFs and epithelial tumor cells and found them to have distinct SE profiles. Next, we explored the role of triptolide (TPL), a natural compound with antitumor activity, in the context of modulating cell-type-specific SE signatures in PDAC. We found that TPL, cytotoxic to both pancreatic tumor cells and CAFs, disrupted SEs in a manner that resulted in the downregulation of SE-associated genes (e.g., BRD4, MYC, RNA Pol II, and Collagen 1) in both cell types at mRNA and protein levels. Our observations suggest that TPL acts as a SE interactive agent and may elicit its antitumor activity through SE disruption to re-program cellular cross talk and signaling in PDAC. Based on our findings, epigenetic reprogramming of transcriptional regulation using SE modulating compounds such as TPL may provide means for effective treatment options for pancreatic cancer patients.

scholarly journals The Function of cGAS-STING Pathway in Treatment of Pancreatic Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Ghazal Mohseni ◽  
Juan Li ◽  
Abakundana Nsenga Ariston Gabriel ◽  
Lutao Du ◽  
Yun-shan Wang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Immune Responses ◽  
Adaptive Immune System ◽  
Type I Interferons ◽  
Pancreatic Tumors ◽  
Type I ◽  
Adaptive Immune ◽  
Combination Methods ◽  
Sting Pathway

The activation of stimulator of interferon genes (STING) signalling pathway has been suggested to promote the immune responses against malignancy. STING is activated in response to the detection of cytosolic DNA and can induce type I interferons and link innate immunity with the adaptive immune system. Due to accretive evidence demonstrating that the STING pathway regulates the immune cells of the tumor microenvironment (TME), STING as a cancer biotherapy has attracted considerable attention. Pancreatic cancer, with a highly immunosuppressive TME, remains fatal cancer. STING has been applied to the treatment of pancreatic cancer through distinct strategies. This review reveals the role of STING signalling on pancreatic tumors and other diseases related to the pancreas. We then discuss new advances of STING in either monotherapy or combination methods for pancreatic cancer immunotherapy.

scholarly journals Role of the Innate Immunity Signaling Pathway in the Pathogenesis of Sjögren’s Syndrome

2021 ◽  
Vol 22 (6) ◽  
pp. 3090
Author(s):  
Toshimasa Shimizu ◽  
Hideki Nakamura ◽  
Atsushi Kawakami
Keyword(s):  
Immune Responses ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Innate Immune ◽  
Type I ◽  
Type I Ifn ◽  
Adaptive Immune ◽  
Sjögren‘S Syndrome

Sjögren’s syndrome (SS) is a systemic autoimmune disease characterized by chronic inflammation of the salivary and lacrimal glands and extra-glandular lesions. Adaptive immune response including T- and B-cell activation contributes to the development of SS. However, its pathogenesis has not yet been elucidated. In addition, several patients with SS present with the type I interferon (IFN) signature, which is the upregulation of the IFN-stimulated genes induced by type I IFN. Thus, innate immune responses including type I IFN activity are associated with SS pathogenesis. Recent studies have revealed the presence of activation pattern recognition receptors (PRRs) including Toll-like receptors, RNA sensor retinoic acid-inducible gene I and melanoma differentiation-associated gene 5, and inflammasomes in infiltrating and epithelial cells of the salivary glands among patients with SS. In addition, the activation of PRRs via the downstream pathway such as the type I IFN signature and nuclear factor kappa B can directly cause organ inflammation, and it is correlated with the activation of adaptive immune responses. Therefore, this study assessed the role of the innate immune signal pathway in the development of inflammation and immune abnormalities in SS.

scholarly journals The dynamic behavior of lipid droplets in the pre-metastatic niche

2020 ◽  
Vol 11 (11) ◽  
Author(s):  
Chunliang Shang ◽  
Jie Qiao ◽  
Hongyan Guo
Keyword(s):  
Tumor Cells ◽  
Immune Cells ◽  
Stromal Cells ◽  
Lipid Droplets ◽  
Metastatic Tumor ◽  
Current Evidence ◽  
Biological Functions ◽  
Metastatic Niche ◽  
Niche Formation

AbstractThe pre-metastatic niche is a favorable microenvironment for the colonization of metastatic tumor cells in specific distant organs. Lipid droplets (LDs, also known as lipid bodies or adiposomes) have increasingly been recognized as lipid-rich, functionally dynamic organelles within tumor cells, immune cells, and other stromal cells that are linked to diverse biological functions and human diseases. Moreover, in recent years, several studies have described the indispensable role of LDs in the development of pre-metastatic niches. This review discusses current evidence related to the biogenesis, composition, and functions of LDs related to the following characteristics of the pre-metastatic niche: immunosuppression, inflammation, angiogenesis/vascular permeability, lymphangiogenesis, organotropism, reprogramming. We also address the function of LDs in mediating pre-metastatic niche formation. The potential of LDs as markers and targets for novel antimetastatic therapies will be discussed.

scholarly journals The Implications of Pruritogens in the Pathogenesis of Atopic Dermatitis

2021 ◽  
Vol 22 (13) ◽  
pp. 7227
Author(s):  
Lai-San Wong ◽  
Yu-Ta Yen ◽  
Chih-Hung Lee
Keyword(s):  
Atopic Dermatitis ◽  
Environmental Factors ◽  
Immune Responses ◽  
Immune Cells ◽  
Inflammatory Disease ◽  
Targeted Therapies ◽  
Skin Barrier ◽  
Skin Barrier Function ◽  
Inflammatory Molecules

Atopic dermatitis (AD) is a prototypic inflammatory disease that presents with intense itching. The pathophysiology of AD is multifactorial, involving environmental factors, genetic susceptibility, skin barrier function, and immune responses. A recent understanding of pruritus transmission provides more information about the role of pruritogens in the pathogenesis of AD. There is evidence that pruritogens are not only responsible for eliciting pruritus, but also interact with immune cells and act as inflammatory mediators, which exacerbate the severity of AD. In this review, we discuss the interaction between pruritogens and inflammatory molecules and summarize the targeted therapies for AD.

scholarly journals TAM Receptor Inhibition–Implications for Cancer and the Immune System

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1195
Author(s):  
Pia Aehnlich ◽  
Richard Morgan Powell ◽  
Marlies J. W. Peeters ◽  
Anne Rahbech ◽  
Per thor Straten
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Cancer Cells ◽  
Immune Cells ◽  
Tyrosine Kinases ◽  
Apoptotic Cell ◽  
Receptor Activation ◽  
Mouse Tumor ◽  
Oncogenic Signaling ◽  
Tam Receptors

Tyro3, Axl and MerTK (TAM) receptors are receptor tyrosine kinases which play important roles in efferocytosis and in the balancing of immune responses and inflammation. TAM receptor activation is induced upon binding of the ligands protein S (Pros1) or growth arrest-specific protein 6 (Gas6) which act as bridging molecules for binding of phosphatidyl serine (PtdSer) exposed on apoptotic cell membranes. Upon clearance of apoptotic cell material, TAM receptor activation on innate cells suppresses proinflammatory functions, thereby ensuring the immunologically silent removal of apoptotic material in the absence of deleterious immune responses. However, in T cells, MerTK signaling is costimulatory and promotes activation and functional output of the cell. MerTK and Axl are also aberrantly expressed in a range of both hematological and solid tumor malignancies, including breast, lung, melanoma and acute myeloid leukemia, where they have a role in oncogenic signaling. Consequently, TAM receptors are being investigated as therapeutic targets using small molecule inhibitors and have already demonstrated efficacy in mouse tumor models. Thus, inhibition of TAM signaling in cancer cells could have therapeutic value but given the opposing roles of TAM signaling in innate cells and T cells, TAM inhibition could also jeopardize anticancer immune responses. This conflict is discussed in this review, describing the effects of TAM inhibition on cancer cells as well as immune cells, while also examining the intricate interplay of cancer and immune cells in the tumor microenvironment.

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