Tumor Biology

, Volume 37, Issue 3, pp 2961–2971 | Cite as

Roles of coinhibitory molecules B7-H3 and B7-H4 in esophageal squamous cell carcinoma

  • Ling Wang
  • Na-na Cao
  • Shan Wang
  • Hong-wei Man
  • Peng-fei Li
  • Bao-en Shan
Original Article


The coinhibitory molecules, B7-H3 and B7-H4, have shown negative regulation in T cell activation and tumor-associated macrophage (TAM) polarization in tumor-specific immunity. Here, we investigated the expression of B7-H3 and B7-H4 in human and murine esophageal squamous cell carcinoma (ESCC) tissues to define their clinical significance and mechanism in a tumor microenvironment. In the present study, B7-H3 and B7-H4 were expressed in 90.6 and 92.7 % samples, respectively. High B7-H3 and B7-H4 expression was associated with advanced TNM stage and lymph node metastasis (p < 0.05, respectively). Patients with both B7-H3 and B7-H4 high-expressed tumors had the poorest prognosis (26.7 months), whereas those with both low-expressed tumors had the best survival (56.7 months). B7-H3 and B7-H4 expression were inclined to be positively related to the infiltration intensity of Treg cells and TAMs (p < 0.05, respectively), and B7-H3 expression is negatively associated with the intensity of CD8+ T cells (p < 0.05). In 4-nitroquinoline 1-oxide (4-NQO)-induced murine models, high B7-H3 expression could only be detected at carcinoma stage, but abnormal B7-H4 expression appeared a little earlier at dysplasia stage. In vitro studies revealed that knockdown of B7-H3 on tumor cells suppressed ESCC cell migration and invasion, while knockdown of B7-H4 could inhibit ESCC cell growth. Overall, B7-H3 and B7-H4 are involved in ESCC progression and development and their coexpression could be valuable prognostic indicators. Interference of these negative regulatory molecules might be a new strategy for treating ESCC.


Coinhibitory molecules Esophageal squamous cell carcinoma B7-H3 B7-H4 



This program was financially supported by the National Natural Science Foundation of China (81173611, 81402228), HeBei Major Medical Scientific Research Foundation (Zd2013045), Hebei Natural Science Foundation (H2015206216), HeBei Province Medical Foundation (ZL20140334), and HeBei Province Education Foundation (QN2014049).

Conflicts of interest


Supplementary material

13277_2015_4132_MOESM1_ESM.pdf (221 kb)
Supplementary figure The detection of B7-H3 (A) and B7-H4 (B) gene expression in Eca-109 cells after siRNA interference via Real-time PCR and western blotting, respectively. GAPDH was used as an internal control. (PDF 221 kb)


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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Ling Wang
    • 1
  • Na-na Cao
    • 2
  • Shan Wang
    • 2
  • Hong-wei Man
    • 1
  • Peng-fei Li
    • 1
  • Bao-en Shan
    • 1
  1. 1.Cancer Research InstituteThe Fourth Hospital of Hebei Medical UniversityShijiazhuangChina
  2. 2.Blood Transfusion DepartmentThe Fourth Hospital of Hebei Medical UniversityShijiazhuangChina

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