B7-H4 expression by nonhematopoietic cells in the tumor microenvironment promotes antitumor immunity.

Cancer Immunol Res 2015 Feb 19;3(2):184-95. Epub 2014 Dec 19.

Campbell Family Institute for Breast Cancer Research, Princess Margaret Cancer Centre, Toronto, Ontario, Canada. Department of Immunology, University of Toronto, Toronto, Ontario, Canada. Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.

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 coinhibitory 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 upregulated 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 that the expression levels of B7-H4 correlate with MHC class I expression in both mouse and human samples. We show that IFNγ upregulates B7-H4 expression on mouse embryo fibroblasts and that the upregulation of B7-H4 on tumors is dependent on T cells. Notably, patients with breast cancer with increased B7-H4 expression show a prolonged time to recurrence. These studies demonstrate a positive role for B7-H4 in promoting antitumor immunity.

Download full-text PDF

Source
http://dx.doi.org/10.1158/2326-6066.CIR-14-0113DOI Listing
February 2015
66 Reads

Publication Analysis

Top Keywords

b7-h4 expression
20
b7-h4
10
antitumor immunity
8
expression mouse
8
role b7-h4
8
immune responses
8
tumor growth
8
expression
6
tumor
5
correlate mhc
4
b7-h4 correlate
4
suitable therapeutic
4
targets b7-h4
4
member inhibits
4
tumorigenesis expression
4
expression levels
4
b7-h4 member
4
members suitable
4
levels b7-h4
4
therapeutic targets
4

Similar Publications