In summary, in this work, we have demonstrated for the first time that: i) IDO suppresses the cross-primed TCD8 response to an immunodominant tumor Ag; ii) IDO-mediated suppression of immunodominant TCD8 is Treg cell- and L-Kyn-independent, and is accompanied by a higher in vivo proliferative capacity of these clones; iii) IDO regulates systemic primary and recall TCD8 responses to influenza. Here, IDO1 is linked to neoplasm.