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.
Highlights
Non-small cell lung cancer (NSCLC) accounts for 80%–85% of all lung cancer cases.[1]
B7-H1/B7-H3 expression in NSCLC tissue samples was associated with lymph node metastasis and advanced TNM stage (p
B7-H1 and B7-H3 were more likely to be expressed in NSCLC cells than in normal lung www.impactjournals.com/oncotarget tissues, and B7-H1/B7-H3 expression was associated with decreased overall survival (OS) in patients with NSCLC
Summary
Non-small cell lung cancer (NSCLC) accounts for 80%–85% of all lung cancer cases.[1]. Immune evasion is recognized as a key feature of cancer progression.[4] Interactions among subsets of immune cells through costimulatory ligands and their receptors are essential for the initiation of an immune response. Further studies revealed that B7-H3 could inhibit the proliferation of T cells in vitro and reduce the secretion of interferon-γ (IFN-γ), tumor necrosis factor-α, granulocyte macrophage colony-stimulating factor, and other cytokines
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