However, the impact of TLO will depend on the nature of the ongoing immune response to the autoantigen, pathogen, or cancer antigen, which may be protective (CD8+ T cells in cancer), inflammatory (Th17 cells in autoimmunity), or tolerance inducing (Foxp3+ regulatory T cells), and this may be regulated by the activation status of PNAd-expressing HEVs and additional factors such as chemokines. The gene discussed is CD8A; the disease is cancer.