Furthermore, most previous studies, whether of human or experimental tumors, did not distinguish tumor antigen-specific from bystander CD4+ T cells, even though bystanders may form most conventional (non-Treg) T cells in the TME (Ahmadzadeh et al., 2019; Azizi et al., 2018; Duhen et al., 2018; Sade-Feldman et al., 2018; Simoni et al., 2018; Zhang et al., 2018; Zheng et al., 2017a) and in draining lymphoid organs where immune responses are typically initiated. This evidence concerns the gene CD4 and neoplasm.