Circulating CD14+HLA-DR-/low myeloid-derived suppressor cells predicted early recurrence of hepatocellular carcinoma after surgery

被引:61
作者
Gao, Xing-Hui [1 ]
Tian, Lu [1 ]
Wu, Jiong [1 ]
Ma, Xiao-Lu [1 ]
Zhang, Chun-Yan [1 ]
Zhou, Yan [1 ]
Sun, Yun-Fan [2 ]
Hu, Bo [2 ]
Qiu, Shuang-jian [2 ]
Zhou, Jian [2 ]
Fan, Jia [2 ]
Guo, Wei [1 ]
Yang, Xin-Rong [2 ]
机构
[1] Fudan Univ, Zhongshan Hosp, Dept Lab Med, 136 Yi Xue Yuan Rd, Shanghai 200032, Peoples R China
[2] Fudan Univ, Zhongshan Hosp, Liver Canc Inst,Dept Liver Surg, Minist Educ,Key Lab Carcinogenesis & Canc Invas, Shanghai, Peoples R China
基金
中国国家自然科学基金;
关键词
hepatocellular carcinoma; myeloid-derived suppressor cells; recurrence; systemic immune-inflammation index; TUMOR PROGRESSION; REGULATORY CELLS; SURVIVAL; INDEX;
D O I
10.1111/hepr.12831
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
AimMyeloid-derived suppressor cells (MDSCs) play an important role in tumor progression. The aim of the present study was to investigate the prognostic value of MDSCs for early recurrence of hepatocellular carcinoma (HCC) in patients undergoing curative resection. MethodsMyeloid-derived suppressor cells were measured by flow cytometry. The correlation between MDSCs and tumor recurrence was analyzed using a cohort of 183 patients who underwent curative resection between February 2014 and July 2015. Prognostic significance was further assessed using Kaplan-Meier survival estimates and log-rank tests. ResultsIn vivo, CD14(+)HLA-DR-/low MDSCs inhibit T cell proliferation and secretion. The frequency of CD14(+)HLA-DR-/low MDSCs was significantly higher in HCC patients (3.75.3%, n=183) than in chronic hepatitis patients (1.4 +/- 0.6%, n=25) and healthy controls (1.1 +/- 0.5%, n=50). High frequency of MDSCs was significantly correlated with recurrence (time to recurrence) (P<0.001) and overall survival (P=0.034). Patients with HCC in the high MDSC group were prone to more vascular invasion (P=0.018) and high systemic immune-inflammation index (SII) (P=0.009) than those in the low MDSC group. Scatter-plot analyses revealed a significant positive correlation between the SII level and the frequency of MDSCs (r=0.188, P=0.011). Patients with HCC with a high MDSC frequency and high SII level had significantly shorter time to recurrence (P<0.001) and overall survival (P=0.028) than those with a low MDSC frequency and low SII. ConclusionsAn increased frequency of MDSCs was correlated with early recurrence and predicted the prognosis of patients with HCC undergoing curative resection. The HCC patients with high frequency of MDSCs should be provided more advanced management and frequent monitoring.
引用
收藏
页码:1061 / 1071
页数:11
相关论文
共 29 条
[1]   Increase in CD14+HLA-DR-/low myeloid-derived suppressor cells in hepatocellular carcinoma patients and its impact on prognosis [J].
Arihara, Fumitaka ;
Mizukoshi, Eishiro ;
Kitahara, Masaaki ;
Takata, Yoshiko ;
Arai, Kuniaki ;
Yamashita, Tatsuya ;
Nakamoto, Yasunari ;
Kaneko, Shuichi .
CANCER IMMUNOLOGY IMMUNOTHERAPY, 2013, 62 (08) :1421-1430
[2]   Systemic Monocytic-MDSCs Are Generated from Monocytes and Correlate with Disease Progression in Breast Cancer Patients [J].
Bergenfelz, Caroline ;
Larsson, Anna-Maria ;
von Stedingk, Kristoffer ;
Gruvberger-Saal, Sofia ;
Aaltonen, Kristina ;
Jansson, Sara ;
Jernstrom, Helena ;
Janols, Helena ;
Wullt, Marlene ;
Bredberg, Anders ;
Ryden, Lisa ;
Leandersson, Karin .
PLOS ONE, 2015, 10 (05)
[3]   Management of Hepatocellular Carcinoma: An Update [J].
Bruix, Jordi ;
Sherman, Morris .
HEPATOLOGY, 2011, 53 (03) :1020-1022
[4]   Clinical significance of plasmacytoid dendritic cells and myeloid-derived suppressor cells in melanoma [J].
Chevolet, Ines ;
Speeckaert, Reinhart ;
Schreuer, Max ;
Neyns, Bart ;
Krysko, Olga ;
Bachert, Claus ;
Van Gele, Mireille ;
van Geel, Nanja ;
Brochez, Lieve .
JOURNAL OF TRANSLATIONAL MEDICINE, 2015, 13
[5]   HIF1α induces the recruitment of bone marrow-derived vascular modulatory cells to regulate tumor angiogenesis and invasion [J].
Du, Rose ;
Lu, Kan V. ;
Petritsch, Claudia ;
Liu, Patty ;
Ganss, Ruth ;
Passegue, Emmanuelle ;
Song, Hanqiu ;
VandenBerg, Scott ;
Johnson, Randall S. ;
Werb, Zena ;
Bergers, Gabriele .
CANCER CELL, 2008, 13 (03) :206-220
[6]   Myeloid-derived suppressor cells in human peripheral blood: Optimized quantification in healthy donors and patients with metastatic renal cell carcinoma [J].
Floercken, Anne ;
Takvorian, Anna ;
Singh, Anju ;
Gerhardt, Anne ;
Ostendorf, Benjamin Nils ;
Doerken, Bernd ;
Pezzutto, Antonio ;
Westermann, Joerg .
IMMUNOLOGY LETTERS, 2015, 168 (02) :260-267
[7]   Hepatocellular carcinoma [J].
Forner, Alejandro ;
Llovet, Josep M. ;
Bruix, Jordi .
LANCET, 2012, 379 (9822) :1245-1255
[8]   Myeloid-derived suppressor cells as regulators of the immune system [J].
Gabrilovich, Dmitry I. ;
Nagaraj, Srinivas .
NATURE REVIEWS IMMUNOLOGY, 2009, 9 (03) :162-174
[9]   Sunitinib pretreatment improves tumor-infiltrating lymphocyte expansion by reduction in intratumoral content of myeloid-derived suppressor cells in human renal cell carcinoma [J].
Guislain, Aurelie ;
Gadiot, Jules ;
Kaiser, Andrew ;
Jordanova, Ekaterina S. ;
Broeks, Annegien ;
Sanders, Joyce ;
van Boven, Hester ;
de Gruijl, Tanja D. ;
Haanen, John B. A. G. ;
Bex, Axel ;
Blank, Christian U. .
CANCER IMMUNOLOGY IMMUNOTHERAPY, 2015, 64 (10) :1241-1250
[10]   Clinical Significance of EpCAM mRNA-Positive Circulating Tumor Cells in Hepatocellular Carcinoma by an Optimized Negative Enrichment and qRT-PCR-Based Platform [J].
Guo, Wei ;
Yang, Xin-Rong ;
Sun, Yun-Fan ;
Shen, Min-Na ;
Ma, Xiao-Lu ;
Wu, Jiong ;
Zhang, Chun-Yan ;
Zhou, Yan ;
Xu, Yang ;
Hu, Bo ;
Zhang, Xin ;
Zhou, Jian ;
Fan, Jia .
CLINICAL CANCER RESEARCH, 2014, 20 (18) :4794-4805