PD-L1 and PD-1 expression correlate with prognosis in extrahepatic cholangiocarcinoma

Abstract

The present study aimed to investigate the clinicopathological significance of programmed cell death ligand-1 (PD-L1) and programmed cell death protein 1 (PD-1) expression in extrahepatic cholangiocarcinoma (ECC). PD-L1 and PD-1 expression was detected by immunohistochemical methods in 70 ECC formalin-fixed, paraffin-embedded tissue specimens and 50 para-carcinoma tissue specimens. The associations of PD-L1 and PD-1 expression with clinicopathological characteristics and prognosis of ECC patients were explored. Positive rates of PD-L1 and PD-1 expression were increased in ECC tissues compared with those in the corresponding para-carcinoma tissues. Besides, the expression of PD-L1 was correlated with the expression of PD-1 (P<0.05). Statistical analysis revealed that the expression of PD-L1 and PD-1 in ECC tissues exhibited no correlation with patient age, sex or histological grade, but was significantly correlated with tumor-node-metastasis (TNM) stage and lymphatic metastasis. Univariate analysis demonstrated that PD-L1 expression, PD-1 expression, TNM stage and lymphatic metastasis were significantly associated with the survival time of patients. Further multivariate analysis revealed the PD-L1 expression was an independent prognostic factor of patients with ECC. These preliminary results suggested that PD-L1 or PD-1 immunodetection may be a valuable prognostic marker for ECC patients, and that PD-L1 immunodetection may be used as an independent factor to evaluate the prognosis of ECC patients.

Programmed cell death ligand‐1 (PD‐L1) expression in extrahepatic biliary tract cancers: a comparative study using 22C3, SP263 and E1L3N anti‐PD‐L1 antibodies

“…In this clinical trial, PD‐L1 positivity was defined as staining in 1% of cells in tumour nests or PD‐L1‐positive bands in the stroma as determined with the 22C3 assay . However, data regarding PD‐L1 expression status in extrahepatic biliary tract cancers are still limited, and the frequency of PD‐L1 expression in bile duct cancer has varied among studies (Table ) . This variability may be explained by multiple factors, including assay method, interpretation method, specimen type (biopsy; surgically resected specimen), and patient demographics (including tumour stage) …”

“…4 However, data regarding PD-L1 expression status in extrahepatic biliary tract cancers are still limited, and the frequency of PD-L1 expression in bile duct cancer has varied among studies (Table 1). [13][14][15][16] This variability may be explained by multiple factors, including assay method, interpretation method, specimen type (biopsy; surgically resected specimen), and patient demographics (including tumour stage). 18,22 Regarding the PD-L1 detection method, currently available tests for PD-L1 expression include commercial assays for clinical trials (22C3, SP263, and SP142), and antibodies labelled as being for research use only (laboratory-developed tests), most commonly the E1L3N antibody.…”

“…12 So far, only four studies have investigated PD-L1 expression in bile duct cancers. The reported frequency of PD-L1 positivity has varied, ranging from 9.1% to 72.2%, [13][14][15][16] and all studies used laboratorydeveloped tests, including the E1L3N assay (Table 1). PD-L1 expression in tumour cells has also been associated with an unfavourable clinical outcome in some studies.…”

“…PD-L1 expression in tumour cells has also been associated with an unfavourable clinical outcome in some studies. 15,16 Herein, we evaluated PD-L1 expression in 183 extrahepatic bile duct cancers, including 89 perihilar and 94 distal bile duct cancers. PD-L1 expression was evaluated with the 22C3, SP263 and E1L3N assays, and the results were compared.…”

The tumour microenvironment and immune milieu of cholangiocarcinoma

“…High expression of PD‐L1 among other immune checkpoints and of tumour‐specific neoantigens characterized a subset of CCA patients (5.9%, 14/239) with high mutational load and poor prognosis . Both PD‐1 and PD‐L1 are up‐regulated in neoplastic cells, and overexpression is associated with increased invasiveness, poor outcome, and worse disease‐ and metastasis‐free survival, especially when accompanied by low CD3 + or CD8 + infiltrate . Conversely, low PD‐L1 expression (in combination with high MHC‐I expression) was found to be related to favourable prognosis .…”