B7-H3 expression associates with tumor invasion and patient's poor survival in human esophageal cancer.

B7-H3, a member from B7-family co-stimulatory ligands, plays an important role in adaptive immune responses. In addition, recent studies also demonstrated that B7-H3 could be highly expressed in various types of human cancers, and its expression level was significantly associated with cancer patients' clinicopathological parameters and postoperative prognoses. As of now, the exact role of B7-H3 expression in human esophageal cancer still remains elusive. In the present study, we characterized the B7-H3 expression in the human esophageal cancer cell line Eca-109 and TE-1, and in 174 cases of human esophageal cancer tissues, and to analyze its clinical implications and its correlation to T cell infiltration. By using the RNA interference method to down-regulate the B7-H3 expression in human esophageal cancer cell line Eca-109, we further studied the contribution of high B7-H3 expression to the biological features of this malignancy. Our results showed that B7-H3 was highly expressed in the cell line Eca-109 and TE-1, the high expression level of B7-H3 in esophageal cancer tissues was significantly associated with tumor invasion and patient's poor survival. Moreover, the higher B7-H3 expression was significantly and inversely correlated to the CD3(+)T cells infiltration in tumor nest of esophageal cancer tissues. We successfully constructed the recombinant lentivirus of siRNA targeting B7-H3, and the cellular studies showed that the down regulation of B7-H3 expression could suppress the proliferation, colony formation, migration and invasion in Eca-109 cells, which was consistent with the finding from the clinical sample cohort study. Collectively, the high B7-H3 expression was involved in the cancer progression of human esophageal cancer, and might contributed to the negative regulation of T-cell mediated antitumor response in tumor microenvironment, and the proliferation and mobility of esophageal cancer cells. The detailed mechanism and the potential value of clinical use targeting B7-H3 against human esophageal cancer merit further investigation.

[1]  Jingting Jiang,et al.  Expression of costimulatory molecules B7-H1, B7-H4 and Foxp3+ Tregs in gastric cancer and its clinical significance , 2015, International Journal of Clinical Oncology.

[2]  H. Kohrt,et al.  Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients , 2014, Nature.

[3]  R. Emerson,et al.  PD-1 blockade induces responses by inhibiting adaptive immune resistance , 2014, Nature.

[4]  X. Luan,et al.  B7-H3 was Highly Expressed in Human Primary Hepatocellular Carcinoma and Promoted Tumor Progression , 2014, Cancer investigation.

[5]  Jingting Jiang,et al.  Higher numbers of T-bet+ intratumoral lymphoid cells correlate with better survival in gastric cancer , 2013, Cancer Immunology, Immunotherapy.

[6]  Xin Zhao,et al.  B7-H3 overexpression in pancreatic cancer promotes tumor progression , 2012, International journal of molecular medicine.

[7]  David C. Smith,et al.  Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. , 2012, The New England journal of medicine.

[8]  B. Seliger,et al.  The expression, function, and clinical relevance of B7 family members in cancer , 2012, Cancer Immunology, Immunotherapy.

[9]  S. Qiu,et al.  B7-H3 is expressed in human hepatocellular carcinoma and is associated with tumor aggressiveness and postoperative recurrence , 2012, Cancer Immunology, Immunotherapy.

[10]  J. Nesland,et al.  B7‐H3 contributes to the metastatic capacity of melanoma cells by modulation of known metastasis‐associated genes , 2012, International journal of cancer.

[11]  Jianquan Hou,et al.  B7-H3 over expression in prostate cancer promotes tumor cell progression. , 2011, The Journal of urology.

[12]  Jingting Jiang,et al.  T-cell-mediated tumor immune surveillance and expression of B7 co-inhibitory molecules in cancers of the upper gastrointestinal tract , 2011, Immunologic research.

[13]  M. Tan,et al.  B7-H4 expression associates with cancer progression and predicts patient’s survival in human esophageal squamous cell carcinoma , 2011, Cancer Immunology, Immunotherapy.

[14]  H. Friess,et al.  B7-H3 and Its Role in Antitumor Immunity , 2010, Clinical & developmental immunology.

[15]  N. Xu,et al.  Immunochemical staining of MT2-MMP correlates positively to angiogenesis of human esophageal cancer. , 2010, Anticancer research.

[16]  V. Reuter,et al.  Tumor associated endothelial expression of B7-H3 predicts survival in ovarian carcinomas , 2010, Modern Pathology.

[17]  N. Xu,et al.  Immunolocalisation of tissue factor in esophageal cancer is correlated with intratumoral angiogenesis and prognosis of the patient. , 2010, Acta histochemica.

[18]  Jingting Jiang,et al.  Clinical significance and regulation of the costimulatory molecule B7-H3 in human colorectal carcinoma , 2010, Cancer Immunology, Immunotherapy.

[19]  M. Takahara,et al.  Expression of B7-H3 in hypopharyngeal squamous cell carcinoma as a predictive indicator for tumor metastasis and prognosis. , 2009, International journal of oncology.

[20]  R. Thompson,et al.  Tumor Cell and Tumor Vasculature Expression of B7-H3 Predict Survival in Clear Cell Renal Cell Carcinoma , 2008, Clinical Cancer Research.

[21]  M. Azuma,et al.  Triggering receptor expressed on myeloid cell-like transcript 2 (TLT-2) is a counter-receptor for B7-H3 and enhances T cell responses , 2008, Proceedings of the National Academy of Sciences.

[22]  Zhao-You Tang,et al.  High expression of macrophage colony-stimulating factor in peritumoral liver tissue is associated with poor survival after curative resection of hepatocellular carcinoma. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[23]  Lieping Chen,et al.  Inhibitory B7-family molecules in the tumour microenvironment , 2008, Nature Reviews Immunology.

[24]  P. Scardino,et al.  B7-H3 and B7x are highly expressed in human prostate cancer and associated with disease spread and poor outcome. , 2008, Proceedings of the National Academy of Sciences of the United States of America.

[25]  G. Stoner,et al.  Chemoprevention of esophageal squamous cell carcinoma. , 2007, Toxicology and applied pharmacology.

[26]  J. Cheville,et al.  B7-H3 ligand expression by prostate cancer: a novel marker of prognosis and potential target for therapy. , 2007, Cancer research.

[27]  Z. Trajanoski,et al.  Type, Density, and Location of Immune Cells Within Human Colorectal Tumors Predict Clinical Outcome , 2006, Science.

[28]  N. Xu,et al.  Immunohistochemical localization of programmed death-1 ligand-1 (PD-L1) in gastric carcinoma and its clinical significance. , 2006, Acta histochemica.

[29]  V. Ling Faculty Opinions recommendation of Molecular characterization of human 4Ig-B7-H3, a member of the B7 family with four Ig-like domains. , 2005 .

[30]  G. Freeman,et al.  The B7–CD28 superfamily , 2002, Nature Reviews Immunology.

[31]  G. Stoner,et al.  Etiology and chemoprevention of esophageal squamous cell carcinoma. , 2001, Carcinogenesis.

[32]  G. Zhu,et al.  B7-H3: A costimulatory molecule for T cell activation and IFN-γ production , 2001, Nature Immunology.

[33]  D. Schottenfeld Epidemiology of cancer of the esophagus. , 1984, Seminars in oncology.

[34]  C. S. Yang,et al.  Research on esophageal cancer in China: a review. , 1980, Cancer research.

[35]  Peter D Siersema,et al.  Esophageal cancer. , 2008, Gastroenterology clinics of North America.

[36]  G. Zhu,et al.  B7-H3: a costimulatory molecule for T cell activation and IFN-gamma production. , 2001, Nature immunology.

[37]  A. Jemal,et al.  Global cancer statistics , 2011, CA: a cancer journal for clinicians.