Ample evidence indicates cancer patients often mount adaptive immune response against cancer, and tumor-specific CD8 effector T cells could infiltrate into tumor lesions. However, these immune responses are often incapable f controlling cancer growth. It is becoming clear in recent years that tumor cells utilize various elaborate tactics to passively reduce their immunogenicity to avoid detection by immune system and to actively induce immune tolerance by surface expression or secreting inhibitory and pro-apoptotic molecules to evade immune system. In the last few years, expression of several B7 family co-signaling molecules, including B7-H1 (Thompson et al., 2006) and B7-H4 (Krambeck et al., 2006), has been linked to accelerated tumor progression and poor prognosis. Furthermore, B7-H1-PD-1 pathway has been vigorously investigated and found to be associated with T-cell dysfunction in chronic infections, including human immunodeficiency virus (HIV) (Day et al., 2006; Trautmann et al., 2006), hepatitis C virus (HCV) (Urbani et al., 2006) and hepatitis B virus (HBV) (Boni et al., 2007). In this chapter, we will focus on the discussion of the mechanisms of B7-H1 and PD-1 pathway in negative regulation of T-cell function and potential therapeutic manipulations targeting B7-H1 in the treatment of cancer and chronic viral infections.
ASJC Scopus subject areas