Gordon J. Freeman, Arlene H. Sharpe& Vijay K. Kuchroo
Suppression of immunological reactivity is one of the major mechanisms by which neoplastic cells are thought to escape host defenses. Tumor-reactive CD4+ and CD8+ T cells can be found in the peripheral blood, lymph nodes and tumors of some tumor-bearing patients, and in some cases, elevated numbers of tumor-infiltrating T lymphocytes (TILs) correlate with better prognosis1. But unfortunately, in most cases tumors continue to grow, suppressing anti-tumor immune responses through mechanisms that are, as yet, not wholly clear. However, it is known that tumors can evade immune attack by downregulating MHC expression on their surface or by producing inhibitory cytokines such as transforming growth factor- (TGF- ) or interleukin-10 (IL-10). In this issue, Dong et al. show that tumors can actively inhibit immune responses by expression of B7 homolog 1 (B7-H1), also known as programmed death ligand 1 (PD-L1)2. B7-H1 is a B7 family member and ligand for programmed death-1 (PD-1), a member of the CD28 family3-6. Receptor-ligand pairs of the B7-CD28 superfamily have key roles in regulating T-cell activation and tolerance7. Dong et al. built on recent findings that B7-H1 is expressed on many tumors5 and examine the consequences of this expression. They report that B7-H1 on tumors can interact with receptors on cytotoxic T lymphocytes (CTLs) and promote CTL death. They then go on to provide a potential avenue for therapy by showing that antibodies against B7-H1 enhance killing of tumor cells by protecting CTLs from B7-H1-induced death.
