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IL-27 induces “stemness” of tumor antigen specific CTLs and promotes CTL survival

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  2. IL-27 induces “stemness” of tumor antigen specific CTLs and promotes CTL survival

IL-27 has been shown to have potent anti-tumor effects involving the induction of anti-tumor cytotoxic T lymphocyte (CTL) responses. However, it remains unclear how IL-27 stimulates CTL responses. Liu et al. report that IL-27 exerts three STAT3 activation-mediated effects on tumor antigen-specific CD8+ T cells, using cells from P1CTL mice, whose CD8+ T cells bear a TCR transgene specific for tumor rejection antigen P1A. First, IL-27 upregulates anti-apoptotic molecule Bcl-2 and inhibits activation of Caspase 3 in activated CTLs, which leads to improved survival of these cells. Second, IL-27 induces a unique stem cell/memory precursor cell (MPC) phenotype in activated CTLs, characterized by the upregulation of SOCS3, Bcl-6 and Sca-1. The authors also show that the IL-27 induced “stemness” of CTLs does not significantly affect their cytotoxicity. Third, IL-27 induces high amounts of IL-10 production by CTLs. IL-27-induced CTL IL-10 production therefore contributes to MPC phenotype, T-cell memory and tumor rejection.

Lui et al., Eur J Immunol 2013;43:468–479.