Cell-type-specific CD73 expression is an independent prognostic factor in bladder cancer

Koivisto, Maarit K; Tervahartiala, Minna; Kenessey, István; Jalkanen, Sirpa; Boström, Peter J.; Salmi, Marko

doi:10.1093/carcin/bgy154

Cited by 30 publications

(23 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…More recently, Koivisto and coworkers demonstrated similar results, expanding the analysis to MI BC. They demonstrated that high expression of CD73 by neoplastic cells was more frequent in NMI than in MI BC [18], a phenomenon not found in our study. In our study, isolated CD73 expression was not su cient to predict the BC stage (Table 4), suggesting the use of isolated CD39 expression or CD39/CD73 expression balance as a useful strategy to access invasive status of the BC.…”

Section: Discussioncontrasting

confidence: 68%

Expression balance of ectoenzymes CD39 and CD73 predicts invasiveness in human bladder cancer

Dellê

Ferreira

Matheus

et al. 2020

Preprint

View full text Add to dashboard Cite

Abstract Background An accurate prediction of progression is critical to define the management of bladder cancer (BC). The ectonucleotidases CD39 and CD73 play strategic roles in calibrating purinergic signals via an extracellular balance between ATP and adenosine. The altered expression of these enzymes plays a potential role in tumor invasion and metastasis, therefore, it has been proposed in the prognosis of solid tumors. In BC this is not yet clear. This study aimed to evaluate CD39 and CD73 expression in a cohort of patients with non-muscle-invasive (NMI) and muscle-invasive (MI) BC regard to its association with clinicopathological features. Methods Retrospective clinical follow-up data and primary urothelial BC specimens of 162 patients were used. Tissue microarrays were constructed, and immunohistochemistry for CD39 and CD73 was performed to make associations with clinicopathological data. Results Overall, 96 were NMI (59.3%) and 66 MI (40.7%). CD39 immunoreactivity in BC cells was found in 72% of the cases, while CD73 was found in 97%. High CD39 expression alone was more frequent in NMI BC (p < 0.001), while high expression of CD73 was more frequent in MI BC. The association of both markers potentiated the prediction, in that high CD39 expression and low CD73 expression was strongly associated with NMI BC and low CD39 with high CD73 was associated with MI BC. Conclusion The invasiveness stage of BC may be predicted by the altered expression of CD39 and CD73. Therefore CD39 serves as an additional tool for the selection of patients with favorable prognosis.

show abstract

Section: Discussioncontrasting

confidence: 68%

Expression balance of ectoenzymes CD39 and CD73 predicts invasiveness in human bladder cancer

Dellê

Ferreira

Matheus

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Bladder cancer is similar. CD73 positive expression by epithelial cells predicts better progression-free survival and overall survival, whereas stromal cell CD73 positivity predicts poor outcome (230). Accordingly, these studies support that CD73 in tumors may suppress and promote tumor progression.…”

Section: Colorectal Cancermentioning

confidence: 52%

CD73's Potential as an Immunotherapy Target in Gastrointestinal Cancers

et al. 2020

View full text Add to dashboard Cite

CD73, a cell surface 5 ′ nucleotidase that generates adenosine, has emerged as an attractive therapeutic target for reprogramming cancer cells and the tumor microenvironment to dampen antitumor immune cell evasion. Decades of studies have paved the way for these findings, starting with the discovery of adenosine signaling, particularly adenosine A2A receptor (A2AR) signaling, as a potent suppressor of tissue-devastating immune cell responses, and evolving with studies focusing on CD73 in breast cancer, melanoma, and non-small cell lung cancer. Gastrointestinal (GI) cancers are a major cause of cancer-related deaths. Evidence is mounting that shows promise for improving patient outcomes through incorporation of immunomodulatory strategies as single agents or in combination with current treatment options. Recently, several immune checkpoint inhibitors received FDA approval for use in GI cancers; however, clinical benefit is limited. Investigating molecular mechanisms promoting immunosuppression, such as CD73, in GI cancers can aid in current efforts to extend the efficacy of immunotherapy to more patients. In this review, we discuss current clinical and basic research studies on CD73 in GI cancers, including gastric, liver, pancreatic, and colorectal cancer, with special focus on the potential of CD73 as an immunotherapy target in these cancers. We also present a summary of current clinical studies targeting CD73 and/or A2AR and combination of these therapies with immune checkpoint inhibitors.

show abstract

“…Cancer associated fibroblasts (CAFs) are an important stromal component in a majority of tumor microenvironments. High levels of CAF CD73 expression is associated with poor prognosis in patients with OC [105] and nonmuscle invasive bladder cancer [106]. CD73-expressing CAFs are also detected in human triple negative breast cancer [107] and OC [108].…”

Section: Myeloid-derived Suppressor Cellsmentioning

confidence: 98%

Cd73: An Emerging Checkpoint for Cancer Immunotherapy

Chen

Wainwright

et al. 2019

Immunotherapy

View full text Add to dashboard Cite

CD73 is a novel immune checkpoint associated with adenosine metabolism that promotes tumor progression by suppressing antitumor immune response and promoting angiogenesis. The inhibition of CD73, in combination with immune checkpoint blockade, targeted therapy or conventional therapy, improves antitumor effects in numerous preclinical mouse models of cancer. Emerging evidence suggests that the combination of anti-CD73 and immune checkpoint blockade has promising clinical activity in patients with advanced solid tumors. In this review, we will discuss the specific role of CD73 on both tumor cells and nontumor cells in regulating tumor immunity and tumorigenesis and provide an update on the current view of the antitumor activity of targeting CD73 by mAb or small molecule selective inhibitors in preclinical and clinical settings.

show abstract

Cell-type-specific CD73 expression is an independent prognostic factor in bladder cancer

Cited by 30 publications

References 42 publications

Expression balance of ectoenzymes CD39 and CD73 predicts invasiveness in human bladder cancer

Expression balance of ectoenzymes CD39 and CD73 predicts invasiveness in human bladder cancer

CD73's Potential as an Immunotherapy Target in Gastrointestinal Cancers

Cd73: An Emerging Checkpoint for Cancer Immunotherapy

Contact Info

Product

Resources

About