This may be either due to the occurrence at the tumor site of a CD28−CD45RA− T-cell population, which lost CD28 following a persistent Ag-mediated local stimulation or be the consequence of an activation eventually occurred when T cells enter in the tumor, congruous with the observation that EM T cells increase only after short-term activation with anti CD3-mAb (Fig. S3B). The gene discussed is CD28; the disease is neoplasm.