Peritumoral plasmacytoid dendritic cells predict a poor prognosis for intrahepatic cholangiocarcinoma after curative res
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PRIMARY RESEARCH
Cancer Cell International Open Access
Peritumoral plasmacytoid dendritic cells predict a poor prognosis for intrahepatic cholangiocarcinoma after curative resection Zhi‑Qiang Hu1,2†, Zheng‑Jun Zhou1,2†, Chu‑Bin Luo1,2, Hao‑Yang Xin1,2, Jia Li1,2, Song‑Yang Yu1,2 and Shao‑Lai Zhou1,2*
Abstract Background: Plasmacytoid dendritic cells (pDCs) are present in various primary and metastatic human neoplasms; however, their clinical significance in intrahepatic cholangiocarcinoma is not clear. Methods: To evaluate pDCs’ distributions in and around tumors as well as their potential function and predictive value for prognosis in patients undergoing curative resection, we performed immunohistochemistry to examine the expression of pDC marker BDCA2, and CD3, CD4, CD8 and Foxp3 in intratumoral and peritumoral tissues from 359 patients with intrahepatic cholangiocarcinoma and compared with prognostic and clinicopathologic factors. Results: Results showed that patients with high numbers of BDCA2+ pDCs in peritumoral tissues were more likely to have elevated levels of carbohydrate antigen 19-9 and gamma-glutamyl transferase, larger and more tumors, advanced tumor-node-metastasis staging, more vascular/bile duct invasion, and lymphatic metastasis in association with greater chance of recurrence and shorter overall survival. Peritumoral tissues with larger numbers of pDCs also showed increased Foxp3+ regulatory T cell infiltration, both of which were found to be independent factors for pre‑ dicting time to recurrence and overall survival. By contrast, patient outcomes were not associated with the presence of intratumoral pDCs. Conclusions: Peritumoral pDC infiltration may indicate an immune tolerogenic peritumor microenviron‑ ment and can be used to predict a poor prognosis for patients undergoing curative resection for intrahepatic cholangiocarcinoma. Keywords: Plasmacytoid dendritic cells, Intrahepatic cholangiocarcinoma, Treg cells, Prognosis, Recurrence
Introduction Intrahepatic cholangiocarcinoma (ICC) is one of most common types of cancer in the liver, second only to hepatocellular carcinoma, and the incidence of ICC continues to increase worldwide [1, 2]. Curative resection for *Correspondence: [email protected] † Zhi-Qiang Hu and Zheng-Jun Zhou contributed equally to this work 1 Liver Surgery Department, Liver Cancer Institute, Zhongshan Hospital, Fudan University, 136 Yi Xue Yuan Road, Shanghai 200032, China Full list of author information is available at the end of the article
ICC relies on early detection, such as by clinical screenings with advanced diagnostic techniques. Nevertheless, the high rate of ICC recurrence shortens the long-term survival of patients [3, 4]. To better predict recurrence in patients after curative resection and enable more effective treatments, the molecular mechanisms contributing to disease recurrence and progression need to be elucidated. The types and densities of immune and nonimmune stromal cells as well as their locations within the tumor microenvironment
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