The third group of the B7-CD28 immune checkpoint family: HHLA2, TMIGD2, B7x, and B7-H3
IMMUNOLOGICAL REVIEWS
Authors: Janakiram, Murali; Shah, Urvi A.; Liu, Weifeng; Zhao, Aimin; Schoenberg, Mark P.; Zang, Xingxing
Abstract
The B7-CD28 family of ligands and receptors play important roles in T-cell co-stimulation and co-inhibition. Phylogenetically they can be divided into three groups. The recent discovery of the new molecules (B7-H3 [CD276], B7x [B7-H4/B7S1], and HHLA2 [B7H7/B7-H5]/TMIGD2 [IGPR-1/CD28H]) of the group III has expanded therapeutic possibilities for the treatment of human diseases. In this review, we describe the discovery, structure, and function of B7-H3, B7x, HHLA2, and TMIGD2 in immune regulation. We also discuss their roles in important pathological states such as cancers, autoimmune diseases, transplantation, and infection. Various immunotherapeutical approaches are emerging including antagonistic monoclonal antibodies and agonistic fusion proteins to inhibit or potentiate these molecules and pathways in cancers and autoimmune diseases.
B7-H7 is a prognostic biomarker in epithelial ovarian cancer
TRANSLATIONAL CANCER RESEARCH
Authors: Fu, Yuanyuan; Ding, Yun; Liu, Juan; Zheng, Xiao; Wei, Wei; Ying, Yaoyu; Wu, Changping; Jiang, Jingting; Ju, Jingfang
Abstract
Background: B7-H7 is a newly identified member of the B7 immune checkpoint family, but has not been investigated in epithelial ovarian cancer (EOC). This study aimed to determine the B7-H7 expression profile and its potential clinical significance in EOC. Methods: A tissue microarray (TMA) containing 160 ovarian cancer tissues was used in this study and 119 EOC cases were valid for analysis. B7-H7 expression was analyzed separately by multiplex immunohistochemistry ( mIHC) staining in different compartment according to tissue segmentation. Correlations of B7-H7 expression and pathological characteristics, including overall survival ( OS) and disease-free survival (DFS), were explored. Results: Multiplex immunohistochemistry staining showed that B7-H7 was broadly expressed in EOC. B7-H7 expression was significantly higher in the tumor compartment than in stromal compartment of EOC. In EOC tissues, B7-H7 expression in tumor compartment was significantly associated with age (P<0.05); B7-H7 expression in stromal compartment was significantly associated with Federation of Obstetrics and Gynecology (FIGO) stage, lymph nodes metastasis, distant metastasis, and OS (all, P<0.05). The KaplanMeier survival analysis revealed that high B7-H7 expression in stromal compartment was significantly correlated with the poor OS of EOC patients (P<0.05), but B7-H7 expression in tumor compartment was not. Conclusions: Stromal B7-H7 expression is significantly associated with tumor progression and prognosis in EOC patients, which might be a prognostic predictor and a potential therapeutic target.