The B7 family plays a critical role in both positive and negative regulation of immune responses by engaging a variety of receptors on lymphocytes. Importantly, blocking co-inhibitory molecules using antibodies specific for CTLA-4 and PD-1 enhances tumor immunity in a subset of patients. Therefore, it is critical to understand the role of different B7 family members since they may be suitable therapeutic targets. B7-H4 is another member that inhibits T-cell function, and it is also up-regulated on a variety of tumors and has been proposed to promote tumor growth. Here we investigate the role of B7-H4 in tumor development and show that B7-H4 expression inhibits tumor growth in two mouse models. Furthermore, we show that B7-H4 expression is required for antitumor immune responses in a mouse model of mammary tumorigenesis. We found the expression levels of B7-H4 correlate with MHC class I expression in both mouse and human samples. We show that IFNγ up-regulates B7-H4 expression on mouse embryo fibroblasts and that the up-regulation of B7-H4 on tumors is dependent on T cells. Notably, breast cancer patients with increased B7-H4 expression show a prolonged time to recurrence. These studies demonstrate a positive role for B7-H4 in promoting antitumor immunity.
- Received June 11, 2014.
- Revision received October 20, 2014.
- Accepted November 11, 2014.
- Copyright © 2014, American Association for Cancer Research.