Considering that a subgroup of CD8+CD28− T cells has been proposed as a distinctive Treg subpopulation [60,61], it has been suggested that it cannot be ruled out that a fraction of intra-tumor CD8+PD1+CD28− T cells may have switched to a Treg-like phenotype, likely driven by the local immunosuppressive milieu [44]. Here, CD28 is linked to neoplasm.