What is the molecular basis for tumor-induced immune suppression?
The tumor cells induce cleavage of the T cell receptor zeta (TCR-z) chain through a caspase-3 dependent manner [12, 13]. This is both FasL-dependent and independent. Since TCR-z is critical for signal transduction, the T cells become unable to respond to tumor antigens. Originally, the suppressed level of TCR-z was described in tumor bearing mice [14, 15] and subsequently in patients. Olivera Finn from University of Pittsburgh described suppressed TCR-z expression in advanced cancer patients [16]. Similar data has been reported for a wide variety of cancers [17-21]. The correlation between suppressed TCR-z and suppressed IFN-g production has also been reported [17]. How does the tumor suppress TCR-z? The cause of TCR-z suppression has been attributed, at least in part, to reactive oxygen radicals produced by: A) The inflammatory activity occurring inside the tumor (it is well established that there is a constant area of necrosis intratumorally B) Macrophages associated with the tumor.
