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.
Department of Pharmacy, Yijishan Affiliated Hospital of Wannan Medical College , Wuhu, Anhui Province, P.R. China.
Zhenyu
Z
Xu
Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University , Luzhou, Sichuan, P.R. China.
Jing
J
Shen
JC School of Public Health and Primary Care, Chinese University of Hong Kong , Hong Kong, P.R. China.
Maggie Haitian
MH
Wang
School of Chinese Medicine, Hong Kong Baptist University , Hong Kong, P.R. China.
Tao
T
Yi
Center for Diabetes, Obesity and Metabolism, Department of Physiology, Shenzhen University Health Science Center , Shenzhen, Guangdong, P.R. China.
Yangyang
Y
Yu
Department of Gastroenterology, the Third Affiliated Hospital of Soochow University , Changzhou, P.R. China.
Yinxin
Y
Zhu
Experiment Center for Medical Science Research, Kunming Medical University , Kunming, Yunnan, P.R. China.
Bo
B
Chen
Department of Breast and Thyroid Surgery, Yijishan Affiliated Hospital of Wannan Medical College , Wuhu, Anhui Province, P.R. China.
Jianping
J
Chen
Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University , Luzhou, Sichuan, P.R. China.
Longfei
L
Li
Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University , Luzhou, Sichuan, P.R. China.
Minxing
M
Li
Department of Pharmacy, Yijishan Affiliated Hospital of Wannan Medical College , Wuhu, Anhui Province, P.R. China.
Jian
J
Zuo
Department of Pharmacy, Yijishan Affiliated Hospital of Wannan Medical College , Wuhu, Anhui Province, P.R. China.
Hui
H
Jiang
Department of Pharmacy, Yijishan Affiliated Hospital of Wannan Medical College , Wuhu, Anhui Province, P.R. China.
Dexi
D
Zhou
Department of Pharmacy, Yijishan Affiliated Hospital of Wannan Medical College , Wuhu, Anhui Province, P.R. China.
Jiajie
J
Luan
Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University , Luzhou, Sichuan, P.R. China.
Zhangang
Z
Xiao
B7 family; CD28 family; breast cancer; cancer immunotherapy; check point