Fig. 7: Macro CD5L+ exacerbated the exhaustion of CD8 GZMB+ in patients with a poor response to GOLP. | Nature Communications

Fig. 7: Macro CD5L+ exacerbated the exhaustion of CD8 GZMB+ in patients with a poor response to GOLP.

From: Macro CD5L+ deteriorates CD8+T cells exhaustion and impairs combination of Gemcitabine-Oxaliplatin-Lenvatinib-anti-PD1 therapy in intrahepatic cholangiocarcinoma

Fig. 7

A The transition trajectory of CD8 proliferating, CD8 GZMB+ and CD8 GZMK+ inferred by RNA velocity analysis of samples from patients with SD and PR (N = 19,128 cells). B Proportion of CD8 GZMB+ with clonal expansion in SD and PR samples. Fisher’s exact test, two-sided. C Distribution of exhausted scores of CD8 GZMB+ in PR and SD samples taken before and after GOLP treatment. Mann–Whitney U test, two-sided, 5631 cells from N = 8 biologically independent patients. D Differentially expressed genes of CD8 GZMB+ between the PR and SD group. Benjamini–Hochberg adjusted P < 0.05 was used as a significance cutoff. t test, two-sided. E Top enriched pathways in CD8 GZMB+ in the PR and SD groups. Benjamini–Hochberg adjusted P < 0.05 was used as a significance cutoff. Hypergeometric test, two-sided. F Dot plot showing the cytokine signaling strength of CD8 GZMB+, CD8 GZMK+, CD8 proliferating and the other 14 myeloid subtypes and tumor clusters (C1-C4), N = 8 paired samples. G CellChat analysis showing the network of cytokine signaling pathways in CD8 GZMB+, CD8 GZMK+, CD8 proliferating and the other 14 myeloid subtypes and tumor meta-clusters (C1-C4). The signal level from Macro CD5L+ was highest among the signals to CD8 GZMB+, and the signal level to CD8 GZMB was highest among the signals from Macro CD5L+. H Scatter plot showing correlations between CD8 GZMB+ and Macro CD5L+ in the FU-iCCA cohort (N = 262) based on signature gene expression. The regression line ± the 95% confidence interval was displayed, Wald test, two-sided. I A representative sample (N = 1 patient) showing crosstalk between CD8 GZMB+ and Macro CD5L+, which were stained by mIHC with anti-CD8 (yellow), anti-GZMB (red), anti-CD68 (white) and anti-CD5L (green) antibodies. Scale bar, 20 μm. J Co-culture strategy of CD8+ T and Macro CD5L+ or the control (Left). The expression of CTLA4, KLRB1 and LAG3 in CD8 GZMB+ after co-culture (Right, t test, two-sided, N = 4 biologically independent experiments for each group). For all boxplots: center line indicates median, box represents first and third quantiles, and whiskers indicate maximum and minimum values. Source data are provided as a Source Data file.

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