title: Clinical significance of B7-H4 expression in matched non-small cell lung cancer brain metastases and primary tumors.
abstract: BACKGROUND
  B7-H4, a member of the inhibitory B7 family, is shown to have a profound inhibitory effect on the proliferation, activation, cytokine secretion, and development of cytotoxicity of T cells and may be involved in immune evasion in cancer patients. Although B7-H4 expression has been detected in non-small cell lung cancer (NSCLC), there are no published reports on the expression of B7-H4 in brain metastases from NSCLC.
  
  
  METHODS
  We examined the expression of B7-H4 by immunohistochemistry in 49 cases of brain metastatic NSCLC, 18 cases of matched primary NSCLC, and 20 cases of NSCLC patients who had neither brain metastases nor other distant metastases.
  
  
  RESULTS
  B7-H4 was highly expressed in 20 (40.8%) out of 49 brain metastases and two (11.1%) out of 18 matched primary tumors. The expression of B7-H4 in brain metastases appeared to be significantly higher than their matched primary tumors (P = 0.016). We also found that patients with high B7-H4 expression in their primary NSCLC have a higher risk of developing brain metastases (P = 0.022). Univariate analyses showed that median overall survival was significantly shorter in patients with high B7-H4 expression in brain metastases (P = 0.002). Multivariate analyses showed that B7-H4 was a significant independent prognostic indicator (P = 0.003).
  
  
  CONCLUSIONS
  NSCLC patients with high B7-H4 expression may benefit from aggressive treatment and close surveillance. Furthermore, our study suggests that B7-H4 may play an important role in the metastatic process of NSCLC and is promising to be a new immune checkpoint molecule for future antitumoral immunotherapy.
authors.affiliation: Beijing Neurosurgical Institute, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Zhen-Ye
authors.initials: ZY
authors.lastname: Li
authors.forename: Xiang-Heng
authors.initials: XH
authors.lastname: Zhang
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.forename: Jian-Gui
authors.initials: JG
authors.lastname: Guo
authors.forename: Ke
authors.initials: K
authors.lastname: Sai
authors.forename: Qun-Ying
authors.initials: QY
authors.lastname: Yang
authors.forename: Zhong-Ping
authors.initials: ZP
authors.lastname: Chen
authors.forename: Yong-Gao
authors.initials: YG
authors.lastname: Mou
keywords: B7-H4; brain metastases; immunotherapy; non-small cell lung cancer