Targeting adenosine and regulatory T cells in cancer immunotherapy

Чуров, А. В.; Zhulai, Galina

doi:10.1016/j.humimm.2020.12.005

Cited by 36 publications

(33 citation statements)

References 67 publications

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“…Adenosine deaminase is a key enzyme in the adenosine catabolism pathway that can affect the immune function of adenosine by regulating the level of extracellular adenosine. Adenosine is considered to be an immunosuppressive molecule that can avoid excessive inflammation [ 11 , 25 , 26 ]. The increased activity of ADA reduces the concentration of adenosine in the peripheral circulation.…”

Section: Discussionmentioning

confidence: 99%

Increased serum adenosine deaminase activity in patients with adult-onset Still's disease

Geng

Guo

et al. 2022

BMC Immunol

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Background Adult-onset Still's disease (AOSD) is a systemic inflammatory disease of unknown etiology, lacking specific diagnosis and disease activity evaluation indicators. This study will analyze the activity and clinical significance of Adenosine deaminase (ADA) in AOSD patients. Methods Totally 53 AOSD patients, 60 patients with other autoimmune diseases including systemic lupus erythematosus (SLE), sjogren syndrome (SS) and rheumatoid arthritis (RA), as well as 60 healthy subjects were included in this study. AOSD activity was determined by Pouchot score. We analyzed the correlation between ADA activity and clinical parameters. In addition, the correlation between ADA activity and disease activity score was also analyzed. Results This study showed that the activity of ADA in AOSD patients was significantly higher than that of healthy controls, SLE, SS and RA patient groups (p < 0.0001). The ADA activity of AOSD patients decreased significantly after systemic treatment (p < 0.0001). Correlation analysis showed that ADA activity was positively correlated with ALT(r = 0.54, p < 0.0001), AST (r = 0.82, p < 0.0001) and serum ferritin (r = 0.67, p < 0.001). ADA activity was negatively correlated with white blood cell (r = − 0.42, p = 0.002) and platelet counts (r = − 0.44, p = 0.001). We also found a significant positive correlation between the activity of ADA and Pouchot score in AOSD patients (r = 0.51, p = 0.001). Receiver operating characteristic (ROC) curve analysis showed that ADA activity had a sensitivity of 93.3%, and a specificity of 83% for the diagnosis of AOSD, with an area under the curve of 0.93. Conclusion This study showed that serum ADA activity can be used as a potential biomarker for AOSD diagnosis and disease activity assessment.

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Section: Discussionmentioning

confidence: 99%

Increased serum adenosine deaminase activity in patients with adult-onset Still's disease

Geng

Guo

et al. 2022

BMC Immunol

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“…These drugs take the form of small-molecule inhibitors or blocking antibodies mainly targeting CD73, CD39, and A2AR (reviewed in ref. 143 ). While these drugs have shown preclinical efficacy in reducing adenosine production and even preventing the ectonucleotidase of soluble forms of CD73 (MEDI9447, also known as oleclumab; ref.…”

Section: Implications For Immunotherapymentioning

confidence: 99%

“…While these drugs have shown preclinical efficacy in reducing adenosine production and even preventing the ectonucleotidase of soluble forms of CD73 (MEDI9447, also known as oleclumab; ref. 144 ), most are awaiting results from phase I/II clinical trials ( 143 ). Interestingly, intraperitoneal treatment of tumor-bearing mice with antisense oligonucleotides targeting CD39 augmented CD8 + T cell proliferation, reduced CD39 expression by tumor and Tregs, and enhanced anti–PD-1 treatment ( 145 ).…”

Section: Implications For Immunotherapymentioning

confidence: 99%

Fighting in a wasteland: deleterious metabolites and antitumor immunity

Watson¹,

Delgoffe²

2022

Journal of Clinical Investigation

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As cancers progress, they produce a local environment that acts to redirect, paralyze, exhaust, or otherwise evade immune detection and destruction. The tumor microenvironment (TME) has long been characterized as a metabolic desert, depleted of essential nutrients such as glucose, oxygen, and amino acids, that starves infiltrating immune cells and renders them dysfunctional. While not incorrect, this perspective is only half the picture. The TME is not a metabolic vacuum, only consuming essential nutrients and never producing by-products. Rather, the by-products of depleted nutrients, “toxic” metabolites in the TME such as lactic acid, kynurenine, ROS, and adenosine, play an important role in shaping immune cell function and cannot be overlooked in cancer immunotherapy. Moreover, while the metabolic landscape is distinct, it is not unique, as these toxic metabolites are encountered in non-tumor tissues, where they evolutionarily shape immune cells and their response. In this Review, we discuss how depletion of essential nutrients and production of toxic metabolites shape the immune response within the TME and how toxic metabolites can be targeted to improve current cancer immunotherapies.

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“…The immunosuppressive activity of Tregs is one of the mechanisms that promote carcinogenesis [95] . The frequency of Foxp3 + Tregs and CD8 + T cells and the density ratio of A2AR + /CD8 + T cells, CD39 + /Foxp3 + Treg and CD73+/Foxp3+Treg were detected by a multiplex immunofluorescence method.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

γδT17/γδTreg cell subsets: a new paradigm for asthma treatment

et al. 2021

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Bronchial asthma (abbreviated as asthma)， is a heterogeneous disease characterized by chronic airway inflammation and airway hyperresponsiveness. The main characteristics of asthma include variable reversible airflow limitation and airway remodeling. The pathogenesis of asthma is still unclear. Th1/Th2 imbalance, Th1 deficiency and Th2 hyperfunction are classic pathophysiological mechanisms of asthma. Some studies have shown that the imbalance of the Th1/Th2 cellular immune model and Th17/Treg imbalance play a key role in the occurrence and development of asthma; however, these imbalances do not fully explain the disease. In recent years, studies have shown that γδT and γδT17 cells are involved in the pathogenesis of asthma. γδTreg has a potential immunosuppressive function, but its regulatory mechanisms have not been fully elucidated. In this paper, we reviewed the role of γδT17/γδTreg cells in bronchial asthma, including the mechanisms of their development and activation. Here we propose that γδT17/Treg cell subsets contribute to the occurrence and development of asthma, constituting a novel potential target for asthma treatment.

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Targeting adenosine and regulatory T cells in cancer immunotherapy

Cited by 36 publications

References 67 publications

Increased serum adenosine deaminase activity in patients with adult-onset Still's disease

Increased serum adenosine deaminase activity in patients with adult-onset Still's disease

Fighting in a wasteland: deleterious metabolites and antitumor immunity

γδT17/γδTreg cell subsets: a new paradigm for asthma treatment

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