Fig. 8: A preferential increase in proliferative CD39⁺ Tpex cells in the blood 2 weeks after ICB therapy is correlated with clinical benefit, and intratumoral CD39⁺ Tpex cells consistently upregulate Ki67 expression following ICB therapy. | Nature Communications

Fig. 8: A preferential increase in proliferative CD39⁺ Tpex cells in the blood 2 weeks after ICB therapy is correlated with clinical benefit, and intratumoral CD39⁺ Tpex cells consistently upregulate Ki67 expression following ICB therapy.

From: Spatial dynamics of CD39+CD8+ exhausted T cell reveal tertiary lymphoid structures-mediated response to PD-1 blockade in esophageal cancer

Fig. 8

a IFN-γ and TNF production by indicated subsets from 18 patients prior to ICB therapy, determined by FC analysis. % IFN-γ and % TNF were compared using a repeated measures ANOVA followed by post-hoc tests with Bonferroni correction (each n = 18, Ki67⁺CD39⁺PD-1⁺ vs. Ki67⁺CD39⁻PD-1⁺ vs. CD39⁻PD-1⁺ T cells). Samples were randomly analyzed. b Representative SLO image of CD39⁺ Tpex cells (open arrowheads). The whole SLO ROI is pseudo-colored as follows: CD3 (green), CD20 (blue), and SMA (red). In the magnified images, the colors are as follows: CD8 (red), PD-1 (green), CD39, TCF-1, TOX (blue), and nuclei (dark blue). This staining pattern is confirmed across three independent SLO samples. White scale bar = 100 μm. c Frequency of CD39⁺ Tpex and CD39⁺ dTex cells among PD-1⁺CD8⁺ T cells pre- vs. post-treatment from 24 patients; two-sided Wilcoxon matched-pairs signed test. CD39⁺ Tpex (Rs: n = 10, NRs: n = 14), CD39⁺ dTex (Rs: n = 10, NRs: n = 14). d % CD39⁺ Tpex cells among CD39⁺Ki67⁺ Tex (total Tex) cells from 24 patients pre-treatment and post-treatment; two-sided Mann-Whitney U-test. Pre-treatment (Rs, n = 10 vs. NRs, n = 14), Post-treatment (Rs, n = 10 vs. NRs, n = 14). e Kaplan-Meier PFS for post-% CD39⁺ Tpex cells among total Tex cells from 28 patients; log-rank test (% CD39⁺ Tpex cells in total Tex cells > 10%, n = 15 vs. < 10%, n = 13). Two cases with missing post-treatment PBMC samples are excluded from the analysis. f ROIs from biopsied tumors of three patients at pre-treatment and around the time of PD on ICB therapy, pseudo-colored as follows: PanCK (white), CD20 (green), CD3 (red), E-cadherin (blue), and nuclei (dark blue). g Density (cells/mm²) of each T cell type in the tumor and stroma pre-treatment (circles) and post-treatment (squares) from three paired tumor-ROIs. h Median nuclear expression of Ki67 in each intratumoral T cell type pre-treatment (circles) and post-treatment (squares) from three paired tumor-ROIs. *P < 0.05, **P < 0.0001. a, d Error bars indicate mean ± SEM. (a, c, d, e) n refers to independent PBMC samples. c, d NE cases and those with missing PBMC samples are excluded from the analysis. h Box plots indicate median values. b was created in BioRender. Kenro, T. (2024) BioRender.com/s50j163. Source data are provided as a Source Data file.

Back to article page