Adenosine deaminase and purine nucleoside phosphorylase activities in peripheral lymphocytes from patients with solid tumours

Russo, Michele; Giancane, R; Apice, Gaetano; Galanti, B

doi:10.1038/bjc.1981.28

Cited by 14 publications

(6 citation statements)

References 17 publications

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“…Since the amount of ADA that can bind to lymphocytes increases with increasing CD26 expression (90,94), activated T cells and NK cells that infiltrate the microenvironment of solid tumors would be predicted to have an increased capacity to deaminate adenosine, thereby ameliorating the inhibitory effect of tumor-associated adenosine. However, this does not appear to be the case as there is ample evidence that ADA activity associated with peripheral lymphocytes from patients with solid tumors is significantly lower than healthy controls (95)(96)(97). Furthermore, it is possible that the high levels of adenosine in the tumor microenvironment (19,20) may down-regulate lymphocyte-associated CD26 and therefore levels of ADA in that context, as has been shown for epithelial cells (37,38).…”

Section: Impact Of Lymphocyte-associated Adenosine Deaminase On Adenomentioning

confidence: 99%

Inhibition of T cell and natural killer cell function by adenosine and its contribution to immune evasion by tumor cells (Review)

Hoskin¹,

Mader²,

Furlong³

et al. 2008

Int J Oncol

168

165

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The resistance of many human cancers to immunebased therapies, including adoptive immunotherapy and the administration of therapeutic cancer vaccines, has been attributed to tumor-associated immune suppression, due in part to immunosuppressive molecules located within the tumor microenvironment. Adenosine is a purine nucleoside found within the interstitial fluid of solid tumors at concentrations that are able to inhibit cell-mediated immune responses to tumor cells. It is well established that extracellular adenosine inhibits T lymphocyte activation and effector function, including T cell adhesion to tumor cells and cytotoxic activity, by signaling primarily through A 2a and A 3 adenosine receptors on the surface of T cells. Importantly, A 2a adenosine receptordeficient mice exhibit enhanced anti-tumor immune responses by CD8 + T cells, as well as a dramatic reduction in the growth of experimental tumors in comparison to wild-type controls. A 2a adenosine receptor signaling has also been implicated in adenosine-mediated inhibition of cytokine production and cytotoxic activity by activated natural killer (NK) cells, although the process of NK cell granule exocytosis is apparently suppressed via a distinct and as yet uncharacterized adenosine receptor. In this report, we review the evidence that adenosine is a potent inhibitor of cellular immune responses and may therefore be a major barrier to the successful immunotherapy of human carcinomas. The signaling pathways through which adenosine exerts its inhibitory effects on cell-mediated immune responses are also discussed. The accumulated evidence suggests that the effectiveness of immune-based therapies for solid tumors may be enhanced by selective antagonism of the adenosine receptor subtypes through which adenosine inhibits the antitumor activity of T lymphocytes and NK cells. Contents

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Section: Impact Of Lymphocyte-associated Adenosine Deaminase On Adenomentioning

confidence: 99%

Inhibition of T cell and natural killer cell function by adenosine and its contribution to immune evasion by tumor cells (Review)

Hoskin¹,

Mader²,

Furlong³

et al. 2008

Int J Oncol

168

165

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“…ADA2 is the main ADA isoenzyme found in human serum [35]. Low ADA activity was found in prostate [38] and gastric tumour tissues [39] and in lymphocytes of patients suffering from different pathologies, such as gynaecological [40], renal [41], head and neck [42], and gastric tumours [43,44], as well as Hodgkin’s lymphoma [45]. Low ADA activity in lymphocytes, as outlined later on in this section, could account for the decreased cellular immune function in cancer patients.…”

Section: Adenosine Deaminasementioning

confidence: 99%

Purine-Metabolising Enzymes and Apoptosis in Cancer

Camici¹,

Garcia‐Gil

Pesi³

et al. 2019

Cancers

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The enzymes of both de novo and salvage pathways for purine nucleotide synthesis are regulated to meet the demand of nucleic acid precursors during proliferation. Among them, the salvage pathway enzymes seem to play the key role in replenishing the purine pool in dividing and tumour cells that require a greater amount of nucleotides. An imbalance in the purine pools is fundamental not only for preventing cell proliferation, but also, in many cases, to promote apoptosis. It is known that tumour cells harbour several mutations that might lead to defective apoptosis-inducing pathways, and this is probably at the basis of the initial expansion of the population of neoplastic cells. Therefore, knowledge of the molecular mechanisms that lead to apoptosis of tumoural cells is key to predicting the possible success of a drug treatment and planning more effective and focused therapies. In this review, we describe how the modulation of enzymes involved in purine metabolism in tumour cells may affect the apoptotic programme. The enzymes discussed are: ectosolic and cytosolic 5′-nucleotidases, purine nucleoside phosphorylase, adenosine deaminase, hypoxanthine-guanine phosphoribosyltransferase, and inosine-5′-monophosphate dehydrogenase, as well as recently described enzymes particularly expressed in tumour cells, such as deoxynucleoside triphosphate triphosphohydrolase and 7,8-dihydro-8-oxoguanine triphosphatase.

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“…12 ADA plays an important role in activation of lymphocytes. 13 Mycobacterial antigens infect macrophages which cause activation of T-cell lymphocytes resulting in increasing levels of ADA in TB. 14 ADA may be released from effusion fluids & be detected in serum of patients with active TB.…”

Section: Introductionmentioning

confidence: 99%

Role of serum adenosine deaminase (ADA) in the diagnosis of tuberculosis & other respiratory diseases

Meshram,

Tadas,

Agarwal

et al. 2023

IJCBR

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: The WHO Tuberculosis (TB) statistics for India in 2021 gave an estimated incidence figure of 25,90,000 cases, i.e., about 40% of Indian population is infected with TB. There are different investigative methods available for TB diagnosis like ZN-staining of ., which lacks sensitivity & another method of Mycobacterial culture takes around 6-8 weeks to isolate . in culture which results in delayed diagnosis & treatment and meanwhile further progression of disease. Other sensitive methods like PCR & CBNAAT are costly & they require skilled personnel & lots of equipment. Therefore, there is a need of simple, cost-effective, rapid & reliable test which can be easily carried out in the clinical laboratories of resource limited countries. In some previous studies, the level of ADA in effusion fluids was used for the diagnosis of TB, but it is not always possible to access effusion fluid & it requires skilled personnel. Thus, the aim of the present study is to evaluate the usefulness of measuring the serum level of ADA as noninvasive biochemical marker in early diagnosis of TB.The present cross-sectional study was conducted on 200 serum ADA samples. Patient samples were divided into four groups based on their diagnosis, i.e., 50 patients with pulmonary TB, 50 patients with extra-pulmonary TB, 50 patients with respiratory infections other than TB & 50 healthy people not having TB. The ADA level for each group was presented as mean + SD & compared by applying post hoc Bonferroni test which showed that the pulmonary TB group was significantly different from the other 3 groups with p<0.001. According to ROC curve analysis, the best cutoff point was 21.8 IU/L at which sensitivity & specificity were 88% & 87% respectively.Serum ADA activity with high sensitivity & specificity percentage can be used as a reliable marker in the diagnosis of TB & to differentiate TB from other respiratory illness.

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Adenosine deaminase and purine nucleoside phosphorylase activities in peripheral lymphocytes from patients with solid tumours

Cited by 14 publications

References 17 publications

Inhibition of T cell and natural killer cell function by adenosine and its contribution to immune evasion by tumor cells (Review)

Inhibition of T cell and natural killer cell function by adenosine and its contribution to immune evasion by tumor cells (Review)

Purine-Metabolising Enzymes and Apoptosis in Cancer

Role of serum adenosine deaminase (ADA) in the diagnosis of tuberculosis & other respiratory diseases

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