Myeloid-derived suppressor cell infiltration is associated with a poor prognosis in patients with hepatocellular carcinoma

髓系抑制细胞浸润与肝细胞癌患者预后不良有关

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作者:Takahiro Tomiyama, Shinji Itoh, Norifumi Iseda, Katuya Toshida, Akinari Morinaga, Kyohei Yugawa, Yukiko Kosai Fujimoto, Takahiro Tomino, Takeshi Kurihara, Yoshihiro Nagao, Kazutoyo Morita, Noboru Harada, Kenichi Kohashi, Yoshinao Oda, Masaki Mori, Tomoharu Yoshizumi

Abstract

The clinicopathological features of myeloid-derived suppressor cell (MDSC) and CD8+ T-cell infiltration in hepatocellular carcinoma (HCC) are poorly understood. The present study examined MDSC and CD8+ T-cell infiltration in surgically resected primary HCC specimens and investigated the association of MDSC and CD8+ T-cell infiltration with clinicopathological features and patient outcomes. Using a database of 466 patients who underwent hepatic resection for HCC, immunohistochemical staining of CD33 (an MDSC marker) and CD8 was performed. High infiltration of MDSCs within the tumor was observed in patients with a poorer Barcelona Clinic Liver Cancer stage, larger tumor size, more poorly differentiated HCC, and greater presence of portal venous thrombosis, microscopic vascular thrombosis and macroscopic intrahepatic metastasis. MDSC infiltration and CD8+ T-cell infiltration were independent predictors of recurrence-free survival and overall survival, respectively. Stratification based on the MDSC and CD8+ T-cell status of the tumors was also associated with recurrence-free survival (10 year-recurrence-free survival; MDSChighCD8+ T-cellLow, 3.68%; others, 25.7%) and overall survival (10 year-overall survival; MDSChighCD8+ T-cellLow, 12.0%; others, 56.7%). In conclusion, the present large cohort study revealed that high MDSC infiltration was associated with a poor clinical outcome in patients with HCC. Furthermore, the combination of the MDSC and tumor-infiltrating CD8+ T-cell status enabled further classification of patients based on their outcomes.

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