Peritumoral plasmacytoid dendritic cells predict a poor prognosis for intrahepatic cholangiocarcinoma after curative resection

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 predicting 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 microenvironment and can be used to predict a poor prognosis for patients undergoing curative resection for intrahepatic cholangiocarcinoma.

The Functional Roles of Immune Cells in Primary Liver Cancer

“…58 High populations of plasmacytoid DCs in the peritumoral area were associated with tumor size, lymphatic metastasis, and poor prognosis in CCA patients, whereas populations of intratumoral plasmacytoid DCs were not, indicating that the functions of DCs may differ depending on the residing location. 59 Because DCs regulate the cytotoxic activity of T cells against tumor cells, DCs can be a therapeutic target for liver cancer. Human DCs were generated from peripheral blood mononuclear cells isolated from healthy donors and were pulsed with cell lysate or total RNAs of human CCA cell lines.…”

Forkhead box M1 recruits FoxP3+ Treg cells to induce immune escape in hilar cholangiocarcinoma

“…The immunosuppressive and immune‐resistant properties of FoxP3 + Treg cells could encourage immune escape, facilitate carcinoma growth, and reverse CD8 + T killing 39 . A growing number of FoxP3 + Treg cells brought about bile duct invasiveness, balanced cancer microenvironment homeostasis, and a high chance of relapse in intrahepatic CCA 40 . The absence of TGF‐β and IL‐2 was related to decreased expression of Foxp3 in Treg cells, thereby influencing different biological and pathological processes 41 .…”

An Integrated Immune-Related Bioinformatics Analysis in Glioma: Prognostic Signature’s Identification and Multi-Omics Mechanisms’ Exploration

“…Plasmacytoid dendritic cells (pDCs) are responsible for creating an immunosuppressive microenvironment in various tumors ( Vermi et al, 2011 ). Peritoneal pDCs infiltration may represent an immune pathogenic pathogen microenvironment and can be used to predict poor prognosis in patients undergoing therapeutic profiling for intrahepatic cholangiocarcinoma ( Hu et al, 2020 ). The above analyses suggest that the poor prognosis of high-risk groups may be closely related to the tumor immunosuppressive environment generated by these immune cells.…”