title: Roles of coinhibitory molecules B7-H3 and B7-H4 in esophageal squamous cell carcinoma.
abstract: 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.
authors.affiliation: Cancer Research Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China.
authors.forename: Ling
authors.initials: L
authors.lastname: Wang
authors.affiliation: Blood Transfusion Department, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China.
authors.forename: Na-Na
authors.initials: NN
authors.lastname: Cao
authors.affiliation: Blood Transfusion Department, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China.
authors.forename: Shan
authors.initials: S
authors.lastname: Wang
authors.affiliation: Cancer Research Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China.
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Man
authors.affiliation: Cancer Research Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China.
authors.forename: Peng-Fei
authors.initials: PF
authors.lastname: Li
authors.affiliation: Cancer Research Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China. baoenshan@hbydsy.com.
authors.forename: Bao-En
authors.initials: BE
authors.lastname: Shan
mesh_terms: D015112:4-Nitroquinoline-1-oxide / Q000633:toxicity; D000328:Adult; D000368:Aged; D000818:Animals; D060887:B7 Antigens / Q000032:analysis / Q000502:physiology*; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000473:pathology*; D045744:Cell Line, Tumor; D004938:Esophageal Neoplasms / Q000139:chemically induced / Q000473:pathology*; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D015363:Quinolones / Q000633:toxicity; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1 / Q000032:analysis / Q000502:physiology*
chemical_list: C120195:4-nitroquinolone-1-oxide; D060887:B7 Antigens; C423237:CD276 protein, human; D015363:Quinolones; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1; C475826:VTCN1 protein, human; D015112:4-Nitroquinoline-1-oxide
keywords: B7-H3; B7-H4; Coinhibitory molecules; Esophageal squamous cell carcinoma