Levels of Circulating PD-L1 Are Decreased in Patients with Resectable Cholangiocarcinoma

Tumor resection represents the only curative treatment option for patients with biliary tract cancers (BTCs), including intrahepatic cholangiocarcinoma (CCA), perihilar and extrahepatic CCA and gallbladder cancer. However, many patients develop early tumor recurrence and are unlikely to benefit from...

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Published in:International journal of molecular sciences 2021-06, Vol.22 (12), p.6569
Main Authors: Roderburg, Christoph, Loosen, Sven H., Bednarsch, Jan, Alizai, Patrick H., Roeth, Anjali A., Schmitz, Sophia M., Vucur, Mihael, Luedde, Mark, Paffenholz, Pia, Tacke, Frank, Trautwein, Christian, Ulmer, Tom F., Neumann, Ulf Peter, Luedde, Tom
Format: Article
Language:English
Subjects:
Apoptosis
Biliary tract
Biology
Biomarkers
Cancer
CCL21 protein
Cell death
Chemokines
Cholangiocarcinoma
Gallbladder cancer
Medical prognosis
Pancreatic cancer
Patients
PD-1 protein
PD-L1 protein
Postoperative period
Prognosis
Regression analysis
Serum levels
Surgery
Tumors
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Summary:Tumor resection represents the only curative treatment option for patients with biliary tract cancers (BTCs), including intrahepatic cholangiocarcinoma (CCA), perihilar and extrahepatic CCA and gallbladder cancer. However, many patients develop early tumor recurrence and are unlikely to benefit from surgery. Therefore, markers to identify ideal surgical candidates are urgently needed. Circulating programmed cell death 1 ligand 1 (PD-L1) has recently been associated with different malignancies, including pancreatic cancer which closely resembles BTC in terms of patients’ prognosis and tumor biology. Here, we aim at evaluating a potential role of circulating PD-L1 as a novel biomarker for resectable BTC. Methods: Serum levels of PD-L1 were analyzed by ELISA in 73 BTC patients and 42 healthy controls. Results: Circulating levels of preoperative PD-L1 were significantly lower in patients with BTC compared to controls. Patients with low PD-L1 levels displayed a strong trend towards an impaired prognosis, and circulating PD-L1 was negatively correlated with experimental markers of promalignant tumor characteristics such as CCL1, CCL21, CCL25 and CCL26. For 37 out of 73 patients, postoperative PD-L1 levels were available. Interestingly, after tumor resection, circulating PD-L1 raised to almost normal levels. Notably, patients with further decreasing PD-L1 concentrations after surgery showed a trend towards an impaired postoperative outcome. Conclusion: Circulating PD-L1 levels were decreased in patients with resectable BTC. Lack of normalization of PD-L1 levels after surgery might identify patients at high risk for tumor recurrence or adverse outcome.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms22126569