Fig. 5. LC improves T cell function in human peripheral blood and cancer tissue.
a, Schematic of experimental design for b–e. b, CD25 expression (left) and IFN-γ in supernatant (right) were detected. n = 6. c, Relative abundance of mitochondrial M + 1 lactate in human CD8+ Teff cells treated with LA and/or LC and 2 mM 2H-LA. n = 5. d, Immunofluorescence staining of MCT1 and COX IV in human CD8+ Teff cells. Scale bar, 5 μm (left). Pearson’s correlation coefficient between MCT1 and COX IV (right). n = 5 cells in LA + LC group and n = 6 cells in other groups examined over three independent experiments. e, Immunoblots of MCT1 and LDHB in human CD8+ Teff cells. f, Schematic of experimental design for h and j. Human CD8+ Teff cells isolated from MPE, colon cancer (CC) and breast cancer (BC) tissue were treated with LC. g, LA concentration in MPE was detected (LAlow < 10 mM, n = 5); LAhigh > 10 mM, n = 7). Peripheral blood (PB) from healthy donors (n = 10) was used as the control. h, Percentage of IL-2+, IFN-γ+, CD107a+and CD137+ cells in CD8+ T cells. n = 5 in LAlow and n = 7 in LAhigh group. i, LA concentration in interstitial fluid of CC (n = 15) and BC (n = 6) tissues. PB from healthy donors (n = 8) was used as the control. j, Percentage of IL-2+, IFN-γ+, CD107a+ and CD137+ cells in CD8+ T cells. n = 6 in BC group and n = 14 in CC group. k, Percentage of transferred human CD45+CD8+ T cells in A375 tumor and CD8+ T in CD45+ cells. n = 5 mice. l, A375 tumor growth of NOG mice administered with LC. n = 6 mice. m, Proposed model for LC-mediated lactate metabolism in CD8+ Teff cells. Created with BioRender.com. Data are presented as the mean ± s.e.m. n = the number of patients/donors unless stated otherwise. P values were calculated using unpaired two-tailed Student’s t-test (k), paired two-tailed Student’s t-test (h), one-way ANOVA for Dunnett’s multiple-comparisons test (b right, c, d, g and i), two-way ANOVA for Sidak’s multiple-comparisons test (l), Kruskal–Wallis test (b, left) and Wilcoxon test (j).