Comprehensive molecular profiling of the B7 family of immune-regulatory ligands in breast cancer

Zhenyu Xu, Jing Shen, Maggie Haitian Wang, Tao YI, Yangyang Yu, Yinxin Zhu, Bo Chen, Jianping Chen, Longfei Li, Minxing Li, Jian Zuo, Hui Jiang, Dexi Zhou, Jiajie Luan*, Zhangang Xiao

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

Abstract

The B7 gene family has crucial roles in the regulation of adaptive cellular immunity. In cancer, deregulation of co-inhibitory B7 molecules is associated with reduced antitumor immunity and cancer immune evasion. FDA approval of cancer immunotherapy antibodies against cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and programmed cell death-1 (PD-1)—both ligands of the B7 family—demonstrate the impact of these checkpoint regulators in cancer. Using data from cBioPortal, we performed comprehensive molecular profiling of the 10 currently known B7 family proteins in 105 different cancers. B7 family members were amplified in breast cancer: with B7 mRNA levels upregulated in a cohort of 1,098 patients with all types of breast cancer and in 82 patients with triple-negative breast cancer. Promoter methylation analysis indicated an epigenetic basis for deregulation of certain B7 family genes in breast cancer. Moreover, patients with B7-H6 genomic alterations had significantly worse overall survival, and certain clinical attributes were associated with B7-H6 expression, which indicates that B7-H6 may be a potential target for breast cancer immunotherapy. Finally, using network analysis (based on data from cBioportal), we identified BTLA, MARCH8, PLSCR1 and SMAD3 as potentially involved in T cell signaling under regulation of B7 family proteins.

Original languageEnglish
Article numbere1207841
JournalOncoImmunology
Volume5
Issue number8
DOIs
Publication statusPublished - 2 Aug 2016

Scopus Subject Areas

  • Immunology and Allergy
  • Immunology
  • Oncology

User-Defined Keywords

  • B7 family
  • breast cancer
  • cancer immunotherapy
  • CD28 family
  • check point

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