Could B7-H4 serve as a target to activate anti-cancer immunity?
It has been over 13years since the identification of B7-H4, the co-stimulatory molecule of B7 family members. While B7-H4 mRNA is widely distributed protein expression seems to be limited on tissues. Various cytokines and inflammatory mediators induce the expression of B7-H4. However, the specific regulatory mechanisms of B7-H4 remain to be defined. Recently, it has been shown that B7-H4 executes an inhibitory function in the T-cell response via reduced expansion, cell cycle arrest, decreased cytokine secretion and induced apoptosis of activated T-cells. Furthermore, B7-H4 suppresses the function of antigen presenting cells (APCs) and promotes the proliferation and development of regulatory T-cells (Treg). Moreover, a growing body of literature demonstrates that various cancers express B7-H4 and that the expression levels of B7-H4 correlate with cancer size, histological type, pathologic stage, grade, infiltration, lymph node metastasis, cancer progression, recurrence and death. The over-expression of B7-H4 in cancer may be related to an increased resistance to immune responses. The aim of this review is to supply an overview of the advances in the regulation and function of B7-H4. Additionally, many studies have suggested that B7-H4 is a molecular target for therapeutic intervention in cancer and that targeting B7-H4 may have promising potential for improving the efficacy of immunotherapy for cancer patients.
Department of Hematology, Hematology Laboratory, Linyi People's Hospital, Shandong University, Linyi, Shandong Province, China. Electronic address: wanglj730@163.com.
Lijuan
L
Wang
Department of Neurosurgery, Linyi People's Hospital, Shandong University, Linyi, Shandong Province, China. Electronic address: hengxy6@163.com.
Xueyuan
X
Heng
Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA. Electronic address: LUY2@ccf.org.
Yong
Y
Lu
Department of Hematology, Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China. Electronic address: caiz@zju.edu.cn.
Zhen
Z
Cai
Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA. Electronic address: yiq@ccf.org.
Qing
Q
Yi
Department of Neurology, Central Laboratory, Linyi People's Hospital, Shandong University, Linyi, Shandong Province, China. Electronic address: che1971@126.com.
Fengyuan
F
Che
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007109:Immunity; D007167:Immunotherapy / Q000379:methods*; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1 / Q000276:immunology / Q000378:metabolism*
D000951:Antigens, Neoplasm; D016207:Cytokines; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1; C475826:VTCN1 protein, human
B7-H4; Cancer; Cancer immune evasion; Cancer immunotherapy; Clinical significance