Fig. 5: Melanoma tumor cells directly alter DC subset metabolism, which dictate DC function. | Nature Communications

Fig. 5: Melanoma tumor cells directly alter DC subset metabolism, which dictate DC function.

From: MCT1 lactate transporter blockade re-invigorates anti-tumor immunity through metabolic rewiring of dendritic cells in melanoma

Fig. 5

PanDCs (mixture of cDC2s, cDC1s and pDCs) purified from HD blood were co-cultured or not with tumor cells from melanoma patients, and further stimulated or not with a mixture of TLR-L. Their metabolism was then studied by flow cytometry using the SCENITH method, and their cytokine/chemokine production was analyzed in supernatants using Luminex. A Experimental design. Created in BioRender. Demars, E. (2025) https://BioRender.com/c00n518. B Heat map displaying the metabolic parameters of DC subsets upon culture or not with tumor cells, and after stimulation (right, Stim; n = 19) or not (left, No stim; n = 23) with TLR-L. C, E Comparative levels of global metabolism (MFI of puromycin) and D, F glycolytic or mitochondrial metabolic dependencies/capacities of DC subsets upon culture (pink circles) or not (blue circles) with tumor cells, in unstimulated (C, D) or stimulated conditions (E, F) (21 donors and 23 tumor lines tested). P-values were calculated using a two-tailed Wilcoxon test (C, E), or non-parametric paired two-way ANOVA (or a mixed effect model) followed by Sidak’s multiple comparison post-tests (D, F - full lines), complemented with Wilcoxon tests (D,F - dashed lines). *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001, ****P ≤ 0.0001. G Comparative PFS (from diagnosis time) and OS (from sampling or diagnosis time) of patients for which cDC2s in co-culture with tumor cells displayed a high or low global metabolism or mitochondrial dependency (10–11 patients per group), or for which stimulated cDC1s in co-culture with tumor cells displayed a high or low global metabolism (9–10 patients per group). Groups were separated using the median value of the corresponding parameter (MFI of puromycin for cDC2s [142756], mitochondrial dependency of cDC2s [36.57%], and MFI of puromycin of stimulated cDC1s [128973]). Comparison was performed using Log-Rank test. *P ≤ 0.05. H Correlation matrix between the metabolic parameters of DC subsets and their cytokine/chemokine production upon co-culture or not with tumor cells (Spearman correlation with Bonferonni corrections for multiple comparisons, n = 37). Stars (*) indicate significant correlations. Only significant statistics are displayed on graphs. Source data are provided as a Source Data file.

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