Fig. 10: Blockade of the MCT1 transporter influences DC-driven naïve T-cell functional and metabolic orientation. | Nature Communications

Fig. 10: Blockade of the MCT1 transporter influences DC-driven naïve T-cell functional and metabolic orientation.

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

Fig. 10

Purified FACS-sorted cDC2s (Lin HLA-DR+ BDCA1+ BDCA3), pre-incubated (green or pink symbols) or not (blue symbols) with BAY-8002 [lactate transporter MCT1 inhibitor] and cultured with NeoGPs functionalized with s-Tn or αFuc motifs, were further cocultured with naïve CD4 or CD8 T cells purified from human cord blood in a 1:10 ratio for 5 days. The phenotypic (activation status, immune checkpoint profile), functional orientation (transcription factors) and metabolic modulations of T cells were then assessed using the SCENITH method combined with surface and intranuclear staining. Cytokine/chemokine secretion profiles were depicted by Luminex in culture supernatants at day 5 and upon 16 h of restimulation with PMA/iono. A Immune checkpoint surface expression on CD4 (left panels) and CD8 (right panels) T cells, n = 6 cocultures. B Intranuclear expression of transcription factors on CD4 (left panels) and CD8 (right panels) T cells, n = 6 cocultures. C Global protein synthesis and metabolic profiles of CD4 T cells assessed in the different conditions using the SCENITH method, n = 7 cocultures. D Cytokine secretion profile at day 5 of coculture, n = 6 cocultures. P-values were calculated using RM two-way ANOVA analysis with Sidak’s multiple comparison post-test. Only significant statistics are displayed on graphs. *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001, ****P ≤ 0.0001. Source data are provided as a Source Data file.

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