CD73 as a prognostic biomarker in human pancreatic cancer
Laakkonen, Joni (2021-02-01)
CD73 as a prognostic biomarker in human pancreatic cancer
(01.02.2021)
Julkaisu on tekijänoikeussäännösten alainen. Teosta voi lukea ja tulostaa henkilökohtaista käyttöä varten. Käyttö kaupallisiin tarkoituksiin on kielletty.
avoin
Julkaisun pysyvä osoite on:
https://urn.fi/URN:NBN:fi-fe202102094209
https://urn.fi/URN:NBN:fi-fe202102094209
Tiivistelmä
Cell surface protein CD73 has important role in sustaining immune homeostasis as the key regulator of extracellular adenosine which mediates immunosuppression and angiogenesis. This CD73 regulated pathway is shown to promote tumor progression and metastases via immune evasion. CD73 is overexpressed in various cancers and usually associated with poor survival, making CD73 a potential next-generation target for cancer immunotherapy. Further research is still needed to better understand, develop and target the immunotherapy.
So far only little is known about CD73 expression in pancreatic ductal carcinoma (PDAC) and its predictive value. The aim of this study was to investigate the prognostic value of CD73 in PDAC and explore its relation to PD-L1, which is a well-known immune checkpoint molecule. The study was conducted using tissue microarray blocks from 110 radically treated patients diagnosed with stage I-IV PDAC. Samples were collected during 2000 to 2016 from the Central Hospital of Central Finland and stained immunohistochemically using CD73 antibody. Quantity and staining intensity of the positive cancer cells, inflammatory cells, stroma and blood vessels were assessed and analyzed together with the clinical patient data.
CD73 positivity in tumor cells had a significant and an independent association with poor disease-specific survival (p=0.021) and overall survival (p=0.016). Furthermore, CD73 positivity in tumor cells did not associate with CD73 positivity in other cell types and had positive association with perineural invasion. PD-L1 expression in tumor cells was associated with CD73 positivity in stroma (p=0.007). CD73 positivity in tumor infiltrating lymphocytes had significant association with lymph node metastasis.
In conclusion, results of this study show that high-level CD73 positivity in PDAC tumor cells is an independent negative prognostic factor and is also associated with perineural invasion. This suggests that patients with PDAC might benefit from anti-CD73 immunotherapy in the future.
So far only little is known about CD73 expression in pancreatic ductal carcinoma (PDAC) and its predictive value. The aim of this study was to investigate the prognostic value of CD73 in PDAC and explore its relation to PD-L1, which is a well-known immune checkpoint molecule. The study was conducted using tissue microarray blocks from 110 radically treated patients diagnosed with stage I-IV PDAC. Samples were collected during 2000 to 2016 from the Central Hospital of Central Finland and stained immunohistochemically using CD73 antibody. Quantity and staining intensity of the positive cancer cells, inflammatory cells, stroma and blood vessels were assessed and analyzed together with the clinical patient data.
CD73 positivity in tumor cells had a significant and an independent association with poor disease-specific survival (p=0.021) and overall survival (p=0.016). Furthermore, CD73 positivity in tumor cells did not associate with CD73 positivity in other cell types and had positive association with perineural invasion. PD-L1 expression in tumor cells was associated with CD73 positivity in stroma (p=0.007). CD73 positivity in tumor infiltrating lymphocytes had significant association with lymph node metastasis.
In conclusion, results of this study show that high-level CD73 positivity in PDAC tumor cells is an independent negative prognostic factor and is also associated with perineural invasion. This suggests that patients with PDAC might benefit from anti-CD73 immunotherapy in the future.