Fig. 5: Slc4a4 targeting unleashes a CD8⁺ T cell-mediated immune response.

a, Percentage of CD8⁺ cells in sgNT (n = 6, 6 and 7) or sgSlc4a4 (n = 6, 5 and 8) subcutaneous Panc02 (left), orthotopic KPC₁ (middle) and KPC₃ tumors (right). b, CD8⁺:T_reg cell ratio in sgNT (n = 5, 6 and 7) and sgSlc4a4 (n = 6, 5 and 8) subcutaneous Panc02 (left), orthotopic KPC₁ (middle) and KPC₃ tumors (right). c,d, Quantification (c) and representative histograms (d) of the MFI of IFNγ (left) and CD69 (right) in CD8⁺ cells in sgNT (n = 5) and sgSlc4a4 (n = 5) subcutaneous Panc02 tumors. FMO: fluorescence minus one. e, MFI of IFNγ (left) and CD69 (right) in CD8⁺ cells in sgNT (n = 6 and 6) and sgSlc4a4 (n = 5 and 7) orthotopic KPC₁ tumors. f, CD8 staining in sgNT (n = 5) and sgSlc4a4 (n = 6) orthotopic Panc02 tumors. g,h, Representative images (g) and quantification (h) of CD8 (red) staining in sgNT (n = 8) and sgSlc4a4 (n = 8) orthotopic KPC₁ tumors. Nuclei are stained with Hoechst (blue). i, MFI of IFNγ (left) and CD69 (right) in CD8⁺ cells in sgNT (n = 6 and 5) and sgSlc4a4 (n = 7 and 5) orthotopic KPC₃ tumors. j, CD8 staining in orthotopic sgNT (n = 8) and sgSlc4a4 (n = 8) KPC₃ tumors. k, Viable (%) Panc02-ovalbumin (Panc02-OVA) cells cocultured with OT-1 T cells in T cell medium (control (Ctrl), n = 3) with lactic acid (Lac; n = 3), HCl (n = 3) or sodium lactate (NaLac; n = 3). l, CD8⁺ T cell proliferation cultured in conditioned medium from sgNT (n = 5) or sgSlc4a4 (n = 5) Panc02 cells supplemented with Lac (n = 6), HCl (n = 6) or NaLac (n = 6); +act, maximal; –act, basal. m, Weight of subcutaneous Panc02 tumors in mice treated with anti-CD8 or control IgG (IgG; sgNT-IgG n = 12, sgSlc4a4-IgG n = 11, sgNT-anti-CD8 n = 5 and sgSlc4a4-anti-CD8 n = 5). n, Weight of orthotopic KPC₁ tumors in mice treated with anti-CD8 or IgG (sgNT-IgG n = 13, sgSlc4a4-IgG n = 13, sgNT-anti-CD8 n = 8 and sgSlc4a4-anti-CD8 n = 7). o, Weight of orthotopic KPC₃ tumors in mice treated with anti-CD8 or IgG (sgNT-IgG n = 15, sgSlc4a4-IgG n = 14, sgNT-anti-CD8 n = 7 and sgSlc4a4-anti-CD8 n = 5). Data in m–o are representative of pools of two independent experiments. n represents independently collected cells (k and l). P value was assessed by unpaired, two-tailed Student’s t-test (a–c, e, f and h–j), two-way ANOVA with Sidak’s multiple comparison test (k), one-way ANOVA with Tukey’s multiple comparison test (l) and two-way ANOVA with Tukey’s multiple comparison test (m–o). Graphs show mean ± s.e.m.; scale bar, 20 μm (g).

Source data