If these PAP-specific CD8+ regulatory responses represent a population of nTreg cells, their presence in the periphery and tumor microenvironment pre- and immediately post-immunization would suppress and prevent the detection of PAP-specific effector responses (as well as potentially induce the generation of IL-35-expressing Tregs), whereas the long-term generation and expansion of effector responses could eventually outnumber these suppressive responses and ultimately lead to the desired goal: the generation of productive, antigen-specific anti-tumor immunity (Figure 2A). This evidence concerns the gene CD8A and neoplasm.