In a recent issue of The Journal of Immunology, Yu and colleagues elegantly describe that IDO is a crucial player for myeloid-derived suppressor cell (MDSC)-mediated suppression of anti-tumor immune responses (1). Hence, they depicted that IDO expression was upregulated in MDSC isolated from fresh breast cancer tissue. Furthermore, IDO was responsible for MDSC-mediated suppression of T cell immunity. Dendritic cells (DC) are additional central cells controlling overactive immunity by regulating immune tolerance. Similar to the MDSC described in the study by Yu et al., IDO-expressing DC have been shown to induce T cell tolerance and to expand regulatory T cells (Tregs) (2). Interestingly, the MDSC in breast cancer tissues correlated with increased infiltration of Tregs in both tumors and lymph node metastasis (1). Recently, the spontaneous presence of IDO-specific, cytotoxic CD8 T cells was described in PBMC from cancer patients (3). Such IDO-specific T cells were able to specifically recognize IDO-expressing DC, thus directly targeting the IDO-dependent counter-regulatory pathway (4). Interestingly, coactivation of IDO-specific cytotoxic T cells boosted tumor-specific T cell immunity; the direct killing of IDO-expressing cells reduced the suppression of effector T cells and decreased the number of Tregs. These findings suggest specific CTL as a new feedback mechanism to suppress immune regulatory cells. The study by Yu et al. puts IDO forward as an even more important immunoregulatory contributor than anticipated and gives additional elucidation for the supportive role of IDO-specific CTL than described in the study by Sørensen et al. (3): the specific targeting of MDSC.
- Copyright © 2013 by The American Association of Immunologists, Inc.
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