School of Chinese Medicine
Comprehensive molecular profiling of the B7 family of immune-regulatory ligands in breast cancer
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.
B7 family, breast cancer, cancer immunotherapy, CD28 family, check point
Source Publication Title
Taylor & Francis
This work was supported by Grants from the National Natural Science Foundation of China (Grant No. 81503093), the University Natural Science Research Project of Anhui Province (Grant No. KJ2016A732) and the Talent Scientific Research Foundation of Yijishan Affiliated Hospital of Wannan Medical College (Grant No. YR201504).
Link to Publisher's Edition
Xu, Zengyu, 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, and Zhangang Xiao. "Comprehensive molecular profiling of the B7 family of immune-regulatory ligands in breast cancer." OncoImmunology 5.8 (2016): Article: e1207841.