NK-cell dysfunction is not rescued by depletion of regulatory T cells or recruitment of ADCC. (A-B) CD4⁺CD25⁺FoxP3⁺ Tregs infiltrate the tumor microenvironment. Effective depletion of Tregs can be achieved after injection of DT every second day into C57BL/6 reconstituted with DEREG or WT control BM; P = .006 for WT mice versus DEREG mice in the NK groups (2-tailed unpaired Student t test). (C) Genetic depletion of Tregs has no effect on tumor growth after NK-cell infusion; ANOVA P = .68. (D) Antibody-mediated depletion of Tregs using the anti-FR4 antibody TH6 does not impact tumor growth after NK-cell infusion. TH6 (anti-FR4) or isotype control were injected intravenously every 3 days beginning day 0 for 2 weeks; ANOVA P = .80. (E) Treatment of SCID mice bearing the human B-cell lymphoma Raji with in vitro expanded human NK cells and rituximab. Mice received tumor with isotype antibody (n = 18) or with rituximab 100 μg (n = 19), NK cells 1 × 10⁷ (n = 14), high-dose NK cells 2 × 10⁷ (n = 5), or NK 1 × 10⁷+ rituximab (n = 18). Results are representative of 2 experiments with 4 to 5 mice per group (A-D) or are a composite of 4 experiments (E).