Defining the mechanisms of CD8 T-cell tumor tolerance.

CD8 T-cell inhibition by myeloid-derived suppressor cells (MDSCs) is one of the presumed methods by which tumors evade the immune system, although the mechanism remains unclear. This paper provides a new insight into the inhibitory interactions between MDSCs and T cells and the mechanisms by which this occurs. The authors demonstrated that tumor-mediated CD8 T-cell suppression via MDSCs causes T cells to be suppressed only for the T-cell receptor (TCR) specific for the tumor-derived antigen while remaining responsive to antigens activating other TCRs in the same cell. They further show that the specific TCR complex is nitrated by the MDSC, which reduces the physical interaction of TCRs with CD3ζ and CD8 and results in lower levels of several TCR-related molecules, including phosphorylated CD3ζ, and reduces activation, proliferation and IFN-γ production in response to the specific antigen of the TCR only. This article will move the field of tumor immunology forward by identifying potential therapeutic targets as well as advancing a mechanistic knowledge to guide further research.