The tumor microenvironment (TME) consists of extracellular matrix proteins, immune cells, vascular cells, lymphatics and fibroblasts. Under normal physiological conditions, tissue homeostasis protects against tumor development. However, under pathological conditions, interplay between the tumor and its microenvironment can promote tumor initiation, growth and metastasis. Immune cells within the TME have an important role in the formation, growth and metastasis of tumors, and in the responsiveness of these tumors to immunotherapy. Recent breakthroughs in the field of cancer immunotherapy have further highlighted the potential of targeting TME elements, including these immune cells, to improve the efficacy of cancer prognostics and immunotherapy. CD38 and CD157 are glycoproteins that contribute to the tumorigenic properties of the TME. For example, in the hypoxic TME, the enzymatic functions of CD38 result in an immunosuppressive environment. This leads to increased immune resistance in tumor cells and allows faster growth and proliferation rates. CD157 may also aid the production of an immunosuppressive TME, and confers increased malignancy to tumor cells through the promotion of tumor invasion and metastasis. An improved understanding of CD38 and CD157 in the TME, and how these glycoproteins affect cancer progression, will be useful to develop both cancer prognosis and treatment methods. This review aims to discuss the roles of CD38 and CD157 in the TME and cancer immunotherapy of a range of solid tumor types.
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http://dx.doi.org/10.3390/cells9010026 | DOI Listing |
Front Immunol
May 2023
Department of Basic Research on Social Recognition and Memory, Research Center for Child Mental Development, Kanazawa University, Kanazawa, Japan.
Nicotinamide adenine dinucleotide (NAD) is a substrate of adenosine diphosphate (ADP)-ribosyl cyclase and is catalyzed to cyclic ADP-ribose (cADPR) by CD38 and/or CD157. cADPR, a Ca mobilizing second messenger, is critical in releasing oxytocin from the hypothalamus into the brain. Although NAD precursors effectively play a role in neurodegenerative disorders, muscular dystrophy, and senescence, the beneficial effects of elevating NAD by NAD precursor supplementation on brain function, especially social interaction, and whether CD38 is required in this response, has not been intensely studied.
View Article and Find Full Text PDFFront Neurosci
July 2022
Department of Biochemistry and Molecular Vascular Biology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.
Investigating the neurocircuit and synaptic sites of action of oxytocin (OT) in the brain is critical to the role of OT in social memory and behavior. To the same degree, it is important to understand how OT is transported to the brain from the peripheral circulation. To date, of these, many studies provide evidence that CD38, CD157, and receptor for advanced glycation end-products (RAGE) regulators of OT concentrations in the brain and blood.
View Article and Find Full Text PDFInt J Mol Sci
April 2022
Department of Biochemistry, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan.
Calcium (Ca) is a ubiquitous and fundamental signaling component that is utilized by cells to regulate a diverse range of cellular functions, such as insulin secretion from pancreatic β-cells of the islets of Langerhans. Cyclic ADP-ribose (cADPR), synthesized from NAD by ADP-ribosyl cyclase family proteins, such as the mammalian cluster of differentiation 38 (CD38), is important for intracellular Ca mobilization for cell functioning. cADPR induces Ca release from endoplasmic reticulum via the ryanodine receptor intracellular Ca channel complex, in which the FK506-binding protein 12.
View Article and Find Full Text PDFEBioMedicine
November 2021
Policlinic of Rheumatology & Hiller Research Unit, Medical Faculty and University Hospital Duesseldorf, Heinrich-Heine-University Düsseldorf, Moorenstr. 5, 40225 Düsseldorf, Germany. Electronic address:
Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that leads to a breakdown of tolerance to self-antigens resulting in inflammation and organ damage. The anti-inflammatory activity of CD73-derived adenosine is well documented, however, its role in SLE pathogenesis is unknown.
Methods: Human peripheral blood immune cells were obtained from adult SLE patients (SLE) and healthy controls (HC).
Sci Rep
August 2021
CCBEF (China Center for Behavior Economics and Finance), Southwestern University of Finance and Economics (SWUFE), Chengdu, China.
Converging evidence suggests that oxytocin (OT) is associated with creative thinking (CT) and that release of OT depends on ADP ribosyl-cyclases (CD38 and CD157). Neural mechanisms of CT and OT show a strong association with dopaminergic (DA) pathways, yet the link between CT and CD38, CD157, dopamine receptor D2 (DRD2) and catechol-O-methyltransferase (COMT) peripheral gene expression remain inconclusive, thus limiting our understanding of the neurobiology of CT. To address this issue, two principal domains of CT, divergent thinking (AUT), were assessed.
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