Abstract
Biliary tract cancer (BTC) refers to a heterogenous group of epithelial malignancies arising along the biliary tree. The highly aggressive nature combined with its silent presentation contribute to the dismal prognosis of this tumor. Tumor-infiltrating immune cells (TIICs) are frequently present in BTC and there is growing evidence regarding their role as therapeutic targets. In this study, we analyzed the immune cell infiltration in BTC and developed a promising immune signature score to predict prognosis in BTC. Immunohistochemistry (IHC) was carried out on tissue microarray sections from 45 patients with resectable cholangiocarcinoma for the detection of 6-sulfoLacNAc+ monocytes (slanMo), BDCA-2+ plasmacytoid dendritic cells (pDC), CD8+ or CD4+T-lymphocytes, CD103+ cells, GATA3+ cells, Toll-like receptor (TLR) 3, 7 and 9-expressing cells as well as programmed cell death protein 1 and programmed cell death ligand 1 positive cells. Data from the IHC staining were analyzed and correlated with clinicopathological and survival data. High expression of TLR7, TLR9, and GATA3 was associated with improved overall survival (OS, Log-rank p < 0.05). In addition, TLR9 was associated with better disease-free survival (Log-rank p < 0.05). In the multivariate Cox proportional-hazards model for OS, the TLR/TLR9/GATA3 score was found to be an independent prognostic factor for OS (“Score 2” vs. “Score 0”: HR 11.17 95% CI 2.27–54.95, p < 0.01).
Highlights
Biliary tract cancer (BTC) comprises a diverse cluster of malignancies that can arise anywhere along the biliary tree, including the gallbladder
The most represented entity was iBTC (38%, n = 17). pBTC was diagnosed in 11 patients (24%). dBTC and GBC were diagnosed in 27% (n = 12) and 11% (n = 5) of the patients, respectively
We performed a comprehensive analysis of tumor-infiltrating immune cells in a cohort of intrahepatic and extrahepatic BTC, including innate immunity members such as TLR7, TLR9, and adaptive immunity factors such as CD4 and CD8 as well as PD1 and Programmed cell death ligand 1 (PD-L1) expression at protein level
Summary
Biliary tract cancer (BTC) comprises a diverse cluster of malignancies that can arise anywhere along the biliary tree, including the gallbladder (gallbladder carcinomas, GBC). This highly heterogeneous group of tumors occurs after a malignant transformation of various cells lining the biliary tract [1]. In Western countries, BTC occurs in 1–2 cases per 100,000 people, whereas in some Eastern countries the incidence is as high as 85 per 100,000 people [3] This discrepancy can be partially explained by the geographical distribution of certain risk factors, such as parasitic infections [4,5]. Many patients with BTC do not have known risk factors [2,6]
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