CD4+ CTLs may kill tumor cells through three potential mechanisms (Fig. 4): First, CD4+ CTLs can recognize homologous antigens presented by APCs and secrete granules to kill target cells in the MHC class II-dependent manner; Second, CD4+ CTLs can upregulate NKG2D to kill tumor cells in the NKG2D-MICA/B pathway-dependent manner; Third, CD4+CD8dim CTLs expressing low levels of CD8 (CD8dim) can kill tumor cells in a MHC class I-dependent manner [55]. This evidence concerns the gene MICA and neoplasm.