Prognositic value of CD73-adenosinergic pathway in solid tumor: A meta-analysis and systematic review

Wang, Rong; Zhang, Yingying; Xia, Lin; Gao, Yalin; Zhu, Ying

doi:10.18632/oncotarget.16905

Cited by 26 publications

(21 citation statements)

References 34 publications

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“…[60] Interestingly, a recent pooled meta-analysis has also suggested the prognostic role of CD73 in many tumors, including some gastrointestinal malignancies. [27] In accordance with these results, in our series, an increased CD73 expression -in terms of percentage of positive cells-was also associated with a reduced overall survival, even if with a very limited impact (HR 1.013). Because CD73 was early identified as an immunoregulatory molecule expressed by lymphocytes, we also evaluated CD73 expression in TIMC.…”

Section: Discussionsupporting

confidence: 90%

“…[26] A potentially adverse prognostic role of CD73 has also been highlighted in a pooled meta-analysis of gene expression analysis and IHC data from studies including ovarian, renal, gastrointestinal, breast and prostate cancer cases and in a study on human malignant melanoma from our group. [27,28] Data generated from public datasets accessible from cBioPortal show consistent CD73 mRNA expression in all investigated tumor types, at variable levels ( Fig. S1).…”

Section: Précismentioning

confidence: 89%

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CD73 expression in normal and pathological human hepatobiliopancreatic tissues

Sciarra

Monteiro

Ménétrier‐Caux

et al. 2019

Cancer Immunol Immunother

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Background: the tumor-expressed CD73 ectonucleotidase generates immune tolerance and promotes invasiveness via adenosine production from degradation of AMP. While anti-CD73 blockade treatment is a promising tool in cancer immunotherapy, a characterization of CD73 expression in human hepatobiliopancreatic system is lacking. Patients and methods: CD73 expression was investigated by immunohistochemistry in a variety of non-neoplastic and neoplastic conditions of the liver, pancreas and biliary tract. Results: CD73 was expressed in normal hepatobiliopancreatic tissues with subcellularspecific patterns of staining: canalicular in hepatocytes, and apical in cholangiocytes and pancreatic ducts. CD73 was present in all hepatocellular carcinoma (HCC), in all pancreatic ductal adenocarcinoma (PDAC), and in the majority of intra and extrahepatic cholangiocellular carcinomas, whereas it was detected only in a subset of pancreatic neuroendocrine neoplasms and almost absent in acinar cell carcinoma. In addition to the canonical pattern of staining, an aberrant membranous and/or cytoplasmic expression was observed in invasive lesions, especially in HCC and PDAC. These two entities were also characterized by a higher extent and intensity of staining as compared to other hepatobiliopancreatic neoplasms. In PDAC, aberrant CD73 expression was inversely correlated with differentiation (p<0.01) and was helpful to identify isolated discohesive tumor cells. Additionally, increased CD73 expression was associated with reduced overall survival (HR 1.013) and loss of E-Cadherin. Conclusions: consistent CD73 expression supports the rationale for testing anti-CD73 therapies in patients with hepatobiliopancreatic malignancies. Specific patterns of expression could also be of help in the routine diagnostic workup.

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Section: Discussionsupporting

confidence: 90%

Section: Précismentioning

confidence: 89%

CD73 expression in normal and pathological human hepatobiliopancreatic tissues

Sciarra

Monteiro

Ménétrier‐Caux

et al. 2019

Cancer Immunol Immunother

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“…CD73 is up-regulated in different types of human solid tumors (reviewed in Ref [ 32 ]). The over-expression of tumor CD73 is in general associated with worse overall survival or progression-free survival, as recently showed in a meta-analysis and systematic review conducted by Wang and collaborators [ 33 ]. CD73 is expressed on the surface of many cell types, including immune cells, endothelial cells, and tumor cells.…”

Section: Introductionmentioning

confidence: 80%

Soluble CD73 as biomarker in patients with metastatic melanoma patients treated with nivolumab

et al. 2017

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BackgroundNivolumab is an anti-PD1 checkpoint inhibitor active in patients with advanced melanoma and as adjuvant therapy in high-risk metastatic melanoma patients.MethodsIn this single-center retrospective analysis, we investigated the CD73 enzyme activity in patients with metastatic melanoma stage IV and its correlation with the response to nivolumab. The soluble CD73 (sCD73) enzyme activity was measured in the serum of 37 melanoma patients before receiving nivolumab and the Harrel’s C index was used to find the best cut-off for this biomarker. The multivariate Cox proportional hazard model was used to evaluate the prognostic value of CD73 enzyme activity for survival and progression-free survival.ResultsOur results show that high levels of sCD73 enzyme activity were significantly associated with poor overall survival and progression-free survival in patients with metastatic melanoma. The median progression–free survival was 2.6 months [95% confidence interval (CI) 1.9–3.3] in patients with high sCD73 enzyme activity (> 27.8 pmol/min/mg protein), and 14.2 months (95% CI 4.6–23.8) in patients with lower CD73 enzyme activity, when patients were follow-up for a median of 24 months range. The median overall survival was not reached in patients with low sCD73 activity (< 27.8 pmol/min/mg protein) compared with 6.1 months (95% CI 0–14.8) in patients with higher sCD73 activity. In multivariate analyses, the sCD73 enzyme activity emerged as the strongest prognostic factor for overall survival and progression-free survival. Elevated basal levels of sCD73 enzyme activity, before starting nivolumab treatment, were associated with lower response rates to therapy.ConclusionsWe observed a significant association between the activity of sCD73 in the blood and clinical outcomes in patients with metastatic melanoma stage IV, receiving nivolumab. Although our results need to be confirmed and validated, we suggest that sCD73 might be used as serologic prognostic biomarker. Potentially evaluating sCD73 enzyme activity in the peripheral blood before treatment could help to estimate the response to nivolumab.

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“…CD73 can also exert a non-enzymatic function as an adhesive and signaling molecule involved in cancer invasion and metastasis. [9][10][11][12][13] CD73 overexpression in cancer cell lines has also been associated with resistance to cytotoxic agents. 9 Soluble CD73, shed from cell membranes, conserves its enzymatic function, was found at higher level in cancer patient compared to heathy volunteer sera, and is associated with resistance to anti-PD-1 therapy in melanoma patients.…”

Section: Introductionmentioning

confidence: 99%

Prognostic value of CD73 expression in resected colorectal cancer liver metastasis

et al. 2020

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Immune checkpoint blockade has not yet been effective in patients with mismatch repair proficient metastatic colorectal cancer. Targeting immunosuppressive metabolic pathways is being explored as a new immunotherapeutic approach. We assessed whether CD73, the rate limiting enzyme that catalyzes the degradation of extracellular AMP into immunosuppressive adenosine, could be an immunological determinant of colorectal liver metastases (CRLMs). By immunofluorescence on tissue microarrays, intratumoral CD73 expression (tCD73) was analyzed in 391 CRLMs resected in 215 patients, and soluble CD73 (sCD73) was measured by ELISA in the pre-operative serum of 193 patients. High tCD73 was associated with worse pathological features, such as multiple and larger CRLMs, and poorer pathologic response to pre-operative chemotherapy. The median time to recurrence and diseasespecific survival after CRLM resection was significantly shorter in patients with high tCD73 (11.0 and 46.4 months, respectively) compared with low tCD73 (19.0 and 61.5 months, respectively). tCD73 was strongly associated with patient outcomes independently of clinicopathological variables. sCD73 did not correlate with tCD73. Patients with high levels of sCD73 also had shorter disease-specific survival. Our results suggested that CD73 in CRLMs may be prognostically informative and may help select patients more likely to respond to adenosine pathway blocking agents.

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Prognositic value of CD73-adenosinergic pathway in solid tumor: A meta-analysis and systematic review

Cited by 26 publications

References 34 publications

CD73 expression in normal and pathological human hepatobiliopancreatic tissues

CD73 expression in normal and pathological human hepatobiliopancreatic tissues

Soluble CD73 as biomarker in patients with metastatic melanoma patients treated with nivolumab

Prognostic value of CD73 expression in resected colorectal cancer liver metastasis

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