Cancer Immunology, Immunotherapy

, Volume 61, Issue 11, pp 2171–2182 | Cite as

B7-H3 is expressed in human hepatocellular carcinoma and is associated with tumor aggressiveness and postoperative recurrence

  • Tai-Wei Sun
  • Qiang Gao
  • Shuang-Jian Qiu
  • Jian Zhou
  • Xiao-Ying Wang
  • Yong Yi
  • Jie-Yi Shi
  • Yong-Feng Xu
  • Ying-Hong Shi
  • Kang Song
  • Yong-Sheng Xiao
  • Jia Fan
Original Article

Abstract

B7-H3, a novel B7 family member, positively or negatively regulates T-cell responses. We investigated the clinical relevance and prognostic significance of B7-H3 in hepatocellular carcinoma (HCC). Western blotting showed B7-H3 upregulation in 17 of 24 (70.8 %) HCC tissues compared with nontumor liver tissues (p = 0.028). B7-H3 immunostaining on tissue microarrays containing 240 HCC patient samples indicated that 225 (93.8 %) tumors had aberrant B7-H3 expression, with strong intensity in 79 (32.9 %) cases, whereas B7-H3 expression in peritumor liver cells was weak in most cases (226; 94.2 %). Notably, patients with high/moderate tumor cell B7-H3 expression showed significantly poorer survival (p = 0.009) and increased recurrence (p = 0.002). After multivariable adjustment, high/moderate B7-H3 expression remained significant for an increased risk of recurrence (hazard ratio = 1.79; 95 % confidence interval = 1.19–2.70; p = 0.005). B7-H3 expression correlated with invasive phenotypes like vascular invasion and advanced tumor stage, and the metastatic potential of HCC cell lines. Flow cytometry showed that B7-H3 expression is inversely correlated with proliferation and interferon-γ production by infiltrating T cells. Interferon-γ stimulation significantly upregulated B7-H3 expression in HCC cells in vitro, implicating B7-H3 expression as a feedback mechanism to evade anti-tumor immunity. Importantly, the prognostic value of B7-H3 expression was validated in an independent cohort of 206 HCC patients. Collectively, our data suggest that B7-H3 was abundantly expressed in HCC and was associated with adverse clinicopathologic features and poor outcome. Thus, B7-H3 represents an attractive target for diagnostic and therapeutic manipulation in human HCC.

Keywords

Hepatocellular carcinoma B7-H3 Prognosis Immunohistochemistry Tumor immunity 

Abbreviations

HCC

Hepatocellular carcinoma

TNM

Tumor-node-metastasis

SD

Standard deviation

OS

Overall survival

TIL

Tumor-infiltrating lymphocytes

HR

Hazard ratio

CI

Confidence interval

Supplementary material

262_2012_1278_MOESM1_ESM.doc (4 mb)
Supplementary material 1 (DOC 4046 kb)
262_2012_1278_MOESM2_ESM.doc (70 kb)
Supplementary material 2 (DOC 70 kb)

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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Tai-Wei Sun
    • 1
    • 4
  • Qiang Gao
    • 1
    • 4
  • Shuang-Jian Qiu
    • 1
    • 4
  • Jian Zhou
    • 1
    • 2
    • 4
  • Xiao-Ying Wang
    • 1
    • 4
  • Yong Yi
    • 1
    • 4
  • Jie-Yi Shi
    • 1
    • 4
  • Yong-Feng Xu
    • 3
  • Ying-Hong Shi
    • 1
    • 4
  • Kang Song
    • 1
    • 4
  • Yong-Sheng Xiao
    • 1
    • 4
  • Jia Fan
    • 1
    • 2
    • 4
  1. 1.Liver Cancer Institute, Zhongshan Hospital and Shanghai Medical SchoolFudan UniversityShanghaiPeople’s Republic of China
  2. 2.Institute of Biomedical SciencesFudan UniversityShanghaiPeople’s Republic of China
  3. 3.Department of Pancreas and Hepatobiliary SurgeryCancer Hospital and Shanghai Medical School, Fudan UniversityShanghaiPeople’s Republic of China
  4. 4.Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of EducationShanghaiPeople’s Republic of China

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