Several mechanisms may account for this finding: (I) killing of lymphocytes by tumor cells expressing proapoptotic ligands, (II) production of immunosuppressive cyto/chemokines by both tumor and tumor stroma cells, (III) presence of CTLA-4-expressing Tregs, (IV) activation-induced cell death of lymphocytes, and (V) immunosuppressive anti-cancer treatments [77,78]. This evidence concerns the gene CTLA4 and neoplasm.