Our single-cell analysis showed that the CD4+ TREG subpopulation (highly expressing FOXP3 and CTLA-4) in DLBCL showed highly immunosuppressive properties, attributed to the eTregs, suggesting that immunotherapy against eTregs could be an effective and novel treatment strategy for DLBCL patients with highly infiltrated FOXP3/CTLA-4 double-positive cells. Here, CD4 is linked to diffuse large B-cell lymphoma.