Malignant T-cell eradication is associated with increased T-cell and NK-effector functions in treated skin. NK and T cells were extracted from lesional skin before and at 8 weeks after resiquimod therapy in 3 HR (1, 3, and 8) and 3 LR (4-6) patients and production of cytokines and effector molecules was evaluated by intracellular cytokine staining and flow cytometry analysis after PMA and ionomycin stimulation. (A-C) Malignant clonal T-cell eradication was associated with high levels of IFN-γ production by both CD4⁺ and CD8⁺ T cells. (A) IFN-γ and IL-17 production by CD4⁺ T cells from patient 3, who had eradication of malignant T cells and a complete clinical response, is shown. Individual patients, before and after resiquimod therapy (B) and aggregate measurements after resiquimod therapy (C) of T-cell IFN-γ production are shown. CD4⁺ T-cell production of IFN-γ was significantly higher in HR patients. (D) Production of TNF-α, perforin, and granzyme by CD4⁺ and CD8⁺ T cells after therapy is shown. Production of TNF-α by CD4⁺ T cells and granzyme by CD8⁺ T cells was significantly higher in HR patients. (E) Increased NK effector functions were associated with clearance of the malignant clone. Production of IFN-γ, perforin, and granzyme by CD56⁺ NK cells is shown. There was a trend for increased NK effector functions in HR patients but given the low number of samples, these differences were not significant. *P < .05, **P < .01.