Abstract
Cholangiocarcinoma is a malignancy arising from the biliary tract epithelial cells with poor prognosis. Tumor infiltrating lymphocytes (TIL)s and programmed cell death receptor ligand 1 (PD-L1) have a prognostic impact in various solid tumors. We aimed to investigate TILs and PD-L1 expression and their clinical relevance in cholangiocarcinoma. Tumor samples from 44 patients with resected and histologically verified extrahepatic cholangiocarcinoma were evaluated for CD8, CD45RO and PD-L1 expression, and their correlations with clinicopathological data and survival data were analyzed. Total 44 extrahepatic cholangiocarcinoma tissues were evaluated. CD8+ tumor infiltrating lymphocytes (TIL)s were observed in 30 (68%) tumors. Among them, 14 had CD8+CD45RO+ TILs. PD-L1 was expressed on cancer cells in 10 (22.7%) tumors in 34 evaluable extrahepatic cholangiocarciniomas. The presence of CD8+ TILs or CD8+CD45RO+ TILs was not associated with clinical staging or tumor differentiation. Extrahepatic cholangiocarcinoma with CD8+CD45RO+ TILs had longer overall survival (OS) on univariate (P = 0.013) and multivariate (P = 0.012) analysis. Neither CD8+TIL nor PD-L1 expression on cancer cells correlated significantly with OS. These results add to the understanding of the clinical features associated with CD8 TILs and PD-L1 expression in extrahepatic cholangiocarcinoma, and they support the potential rationale of using PD-1 blockade immunotherapy in cholangiocarcinoma.
Highlights
Cholangiocarcinoma is a rare cancer originating from the epithelial cells of the intrahepatic and extrahepatic bile ducts
Neither CD8+Tumor infiltrating lymphocytes (TIL) nor programmed cell death receptor ligand 1 (PD-L1) expression on cancer cells correlated significantly with overall survival (OS). These results add to the understanding of the clinical features associated with CD8 TILs and PD-L1 expression in extrahepatic cholangiocarcinoma, and they support the potential rationale of using programmed cell death 1 (PD-1) blockade immunotherapy in cholangiocarcinoma
The recent success of PD-1 blockade immunotherapy has led to extensive studies to discover predictive markers in tumor microenvironment of several malignancies
Summary
Cholangiocarcinoma is a rare cancer originating from the epithelial cells of the intrahepatic and extrahepatic bile ducts. Cholangiocarcinoma is an uncommon malignancy accounting for approximately 3% of all gastrointestinal tumors [1]. It is a very aggressive group of malignancies with overall dismal prognosis. The 5 year survival rate is only 10% [2]. While local treatment such as surgical resection is effective for localized disease, treatment of recurrent or metastatic disease is quite challenging. Gemcitabine plus cisplatin has demonstrated a significant antitumor activity as firstline therapy for metastatic cholangiocarcinoma [3], new effective therapeutic approaches are needed for further improvement of clinical outcome
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