Fig. 7
Prognostic significance of CD45RA−FOXP3highCD4+ T cells (eTreg cells) in TILs. a Kinetic changes (% of change from the base line) in eTreg cells according to clinical response. In all 5 PR patients, eTreg cells in TILs were decreased at the PR stage compared with pre-treatment, whereas no trend was observed between the PR and PD stages (1 increased from PR to PD; 2 decreased from PR to PD). In 9 SD patients, no trend was observed in terms of eTreg-cell kinetic changes. In all 3 patients who experienced PD at the first evaluation, eTreg cells in TILs were decreased at the PD stage compared with the pre-treatment time point. The averages were used if more than one samples at post-treatment were available. b Kinetic changes (% of change from the base line) in PD-1 expression by CD8+ T cells according to clinical responses. In almost all patients, PD-1 expression by CD8+ T cells in TILs were decreased following treatment; this did not correlate with the clinical response. c eTreg cells and clinical outcomes. Patients with PR had a significantly higher frequency of eTreg cells in TILs than those with PD (32.56 ± 12.11% vs. 14.83 ± 3.18%; P = 0.036), whereas no significant difference was observed between patients with PR and SD or SD and PD (32.56% ± 12.11% vs. 20.32% ± 9.28%, P = 0.094 and 20.32% ± 9.28% vs. 14.83% ± 3.18%, P = 0.14). Patients with a high frequency of eTreg cells in pre-treatment TILs had a significantly longer PFS than those with a low frequency (161 days vs. 76 days; hazard ratio, 0.30; P = 0.032). d PD-1 expression by CD8+ T cells and clinical responses. Both patients with PR and patients with SD tended to have a lower PD-1 expression by CD8+ T cells in TILs than those with PD (46.00% ± 22.65% and 54.23% ± 17.11% vs. 72.50% ± 8.97%, P = 0.067 and 0.051, respectively), but the difference was not significant. No significant difference was observed in the PFS between patients with a high PD-1 expression by CD8+ T cells in pre-treatment TILs and those with a low expression (118.5 days vs. 110 days; hazard ratio, 0.83; P = 0.72). n.s., not significant