Fig. 7: ASO-Snrnp200 synergistic immunotherapy amplifies the antitumor response in glycolytic tumors.

a Schematic outline showing Snrnp200-targeted ASO treatment or LDH inhibition combined with anti-PD-1 antibody treatment of tumors: 5 × 10⁵ 4T1 mouse breast cancer cells were subcutaneously injected into BALB/c mice. When the tumors reached 50–100 mm³, the mice were treated with ASO-Snrnp200 (5 mg/kg subcutaneous injection, twice a week, n = 6 mice/group), FX-11 (2 mg/kg daily i.p. injection, daily), or PBS (50 µL, i.p. injection, daily) for 2 weeks combined with an isotype control or anti-PD-1 antibody (10 mg/kg, i.p. injection, twice a week). b, c Relative lactic acid (b) and GSH (c) levels in the six treatment groups. The data are presented as the mean ± SEM. d Tumor growth in different groups. The data are presented as the mean ± SEM. e, f Primary tumors from 4T1 model mice were harvested for flow cytometry to determine the percentages of CD8⁺ T cells among CD3⁺ T cells (e) and of Treg cells among CD4⁺ T cells (f). g The expression of PD-1 by CD8⁺ T cells (top) and Treg cells (bottom) in the tumor microenvironment was examined. Representative histograms and summary data are shown. The data are presented as the mean ± SEM. h Representative histogram plots showing GZMB⁺ and IFN-γ⁺ cells among CD8⁺ T cells. i Representative histogram plots showing CTLA4⁺, ICOS⁺, and GITR⁺ cells among Treg cells. j Representative multiplexed immunohistochemistry images of PD1⁺CD8⁺ T cells (top) and PD1⁺CD4⁺FOXP3⁺ T cells (bottom) in the TME. Scale bars, 100 μm or 40 μm. For b–g, the data were compared using Student’s t-test if the data in each group were normally distributed (n = 6 mice/group; *P < 0.05; **P < 0.01; ***P < 0.001; ns not significant, P > 0.05).