Fig. 3

Inverse correlation between the presence of anti-TERT CD4⁺ Th1 response and the level of exhausted PD-1⁺TIM-3⁺ T cells. a, b Levels of circulating PD-1⁺ and/or TIM-3⁺ CD4⁺ T cells (a) and CD8⁺ T cells (b) in patients with anti-TERT Th1 response (n = 49) and in non-responders (n = 96) (Mann–Whitney test). c, d Levels of circulating PD-1⁺ and/or TIM-3⁺ CD4⁺ T cells (c) and CD8⁺ T cells (d) in patients with antiviral Th1 response (n = 116) and in non-responders (n = 28) (Mann–Whitney test). Box spans indicate median and 25th–75th percentile, whiskers indicate the highest/lowest datapoints. e Dot plots show Ki-67 staining of unstimulated PBMC from one representative patient. f, g Blood lymphocytes from patients were stimulated with TERT-derived peptides with or without blocking mAb against PD-L1, PD-1 and/or TIM-3. TERT-specific T cells were measured by ICS or ELISpot. f Histograms show IFN-γ spot-forming cells from three representative patients. g In left, representative dot plot of TNF-α and IFN-γ-producing CD4⁺ T cells; In right, percentage of IFN-γ and TNF-α-secreting anti-TERT CD4 + T cells (n = 6). The data are representative of three independent experiments. *P < 0.05; **P < 0.01. ns not significant