Fig. 5: NK cells exhibit an exhausted phenotype in long survivors.

a, b Representative flow cytometry staining (left) for PD-1 (a) and LAG-3 (b) in NK cells and summaries (right) for the frequencies of NK cells at pre-mogamulizumab treatment (PD-1, p = 0.197 and LAG-3, p = 0.3095) in long survivors (≥1 year) and short survivors (< 1 year) are shown. PBMC samples (long survivors: n = 6, short survivors: n = 6), as in Fig. 4, were subjected to flow cytometry. c The distinct ADCC activity by exhausted NK cells. LAG-3^-PD-1^-, LAG-3⁺PD-1^- and LAG-3⁺PD-1⁺ NK cells derived from PBMCs of healthy individuals (n = 5) were co-cultured with CD4⁺ T cells in the presence of mogamulizumab, and reduction of eTreg cells was examined. Representative flow cytometry data (left) and summary for depletion efficacy of eTreg cells (LAG-3⁺PD-1^- NK cells, *p = 0.0159 and LAG-3⁺PD-1⁺ NK cells, **p = 0.0079) are shown (right). d The frequencies of CCR4-expressing cells (top) and expression levels (mean fluorescence intensity: MFI) of CCR4 (bottom) in each CD8⁺ T cell fraction and eTreg cells in PBMCs from healthy individuals (n = 7). The differences between each CD8⁺ T cell fraction and eTreg cells were ***p < 0.0001 in the frequencies and the expression levels. The differences between central memory CD8⁺ T cells and Naive CD8⁺ T cells, and effector memory CD8⁺ T cells, and TEMRA CD8⁺ T cells were **p = 0.0027, *p = 0.017 and **p = 0.0024, respectively in the frequencies of CCR4-expressing cells; were *p = 0.0286, **p = 0.0059 and *p = 0.0211, respectively in the expression levels of CCR4. e Reduction of central memory CD8⁺ T cells (left) and eTreg cells (right) after mogamulizumab treatment. PBMC samples from healthy individuals (n = 12) were cultured with the indicated dose of mogamulizumab. Changes in each T cell fraction were examined (10 µg/mL, *p = 0.043 in central memory CD8⁺ T cells and 10–0.00001 µg/mL, ***p < 0.0001 in eTreg cells). In (a and b), black dots, patients who received 1.0 mg/kg mogamulizumab; blue dots patients who received 0.1 mg/kg mogamulizumab. Naive CD8⁺ T cells: Naive, central memory CD8⁺ T cells: Central memory, effector-memory CD8⁺ T cells: Effector memory, TEMRA CD8⁺ T cells: TEMRA. In (a and b), one-sided Mann–Whitney test was used. In (c), two-sided Mann–Whitney test was used. In (d and e), two-sided Dunnett test was used. In (e), the center line indicates the median, and the box limits indicate the 1st and 3rd quartiles. The whiskers go down to the smallest value and up to the largest. *p < 0.05, **p < 0.005, ***p < 0.0001. Source data are provided as a Source Data file.