Programmed Death-Ligand 1 (PD-L1) Expression Associated with a High Neutrophil/Lymphocyte Ratio in Cholangiocarcinoma

Abstract

<br /> <strong><span style="font-size: small;">Background: </span></strong><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">Effective treatments for cholangiocarcinoma (CCA) are still lacking. There are promising results of checkpoint inhibitor programmed cell death ligand-1 (PD-L1) activities in early phase trials. This study aimed to investigate the expression of PD-L1 and its relation to possible treatments for CCA. </span></span><strong><span style="font-size: small;">Methods: </span></strong><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">Formalin-fixed paraffin-embedded tumor samples from 46 patients with cholangiocarcinoma were retrieved. PD-L1 expression was </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">evaluated by immunohistochemistry using anti-PD-L1 antibody, clone 5H1. A PD-L1 positive response on tumor cells </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">was defined as >1% of tumor cell membranes stained. The association between PD-L1, clinico-pathological characteristics </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">was analyzed using Fisher's exact test, and survival analysis was done with the Cox regression model. </span></span><strong><span style="font-size: small;">Results: </span></strong><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">Out of 46 samples, 32 (70%) had positive PD-L1 expression in tumor cell membranes. The median level of PD-L1 expression </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">was 1.75% (0-34.7). PD-L1 expression was significantly associated with stage IV disease (OR 3.98, p=0.046) and a high neutrophil/lymphocyte ratio (OR 5.36, p=0.018). PD-L1 positivity was associated with worse overall survival compared with those with a PD-L1 negative tumor but did not reach a level of significance (7.2 vs. 7.9 months, p=0.32). </span></span><strong><span style="font-size: small;">Conclusion: </span></strong><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">PD-L1 is widely expressed in CCA but was not predictive for overall survival. PD-L1 positivity was </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">(7.2 and 7.9 months, p=0.32). Significantly associated with stage IV disease and a high neutrophil/lymphocyte ratio. </span></span>