B7-H1 and B7-H3 are independent predictors of poor prognosis in patients with non-small cell lung cancer

// Yixiang Mao 1,* , Wei Li 1,* , Kai Chen 1 , Yufeng Xie 1 , Qiang Liu 2 , Min Yao 3 , Weiming Duan 1 , Xiumin Zhou 1 , Rongrui Liang 1 and Min Tao 1,4 1 Department of Oncology, the First Affiliated Hospital of Soochow University, Suzhou, China 2 Department of Pathology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China 3 Department of Pathology, Punan Hospital, Shanghai, China 4 Jiangsu Institute of Clinical Immunology, Suzhou, China * These authors contributed equally to this work Correspondence: Min Tao, email: // Keywords : B7-H1, B7-H3, non-small cell lung cancer, prognosis Received : November19, 2014 Accepted : December 25, 2014 Published : December 31, 2014 Abstract B7-H1 and B7-H3, two members of the B7 family that are thought to regulate T-cell activation, are expressed in human non-small cell lung cancer (NSCLC). However, their prognostic significance is poorly understood. In the present study we reported that B7-H1 and B7-H3 were expressed in 96/128 (72.7%) and 89/128 (69.5%) samples, respectively. B7-H1 and B7-H3 expression and the number of infiltrating T-cell intracellular antigen-1+ and interferon-γ+ cells in NSCLC tissues were significantly higher than those in the adjacent tissues (p<0.01). High B7-H1 or B7-H3 expression was associated with lymph node metastasis and TNM stage (p<0.05, respectively). Sex, TNM stage, B7-H1, B7-H3, and T-cell intracellular antigen-1 expression remained significant prognostic factors after adjusting for other prognostic factors in a multivariate Cox proportional hazards regression model. In vitro studies revealed that knockdown of B7-H3 on tumor cells enhanced T-cell growth and interferon-γ secretion when stimulated by anti-CD3 and anti-CD28 monoclonal antibodies. Interferon-γ reduced CXCR4 expression on cancer cells and inhibited the CXCL12-induced cell migration.B7-H1 and B7-H3 are independent predictors of poorer survival in patients with NSCLC. Interference of the signal pathways of these negative regulatory molecules might be a new strategy for treating NSCLC.