Journal: Oncogene
Article Title: Methylmalonic acid induces metabolic abnormalities and exhaustion in CD8 + T cells to suppress anti-tumor immunity
doi: 10.1038/s41388-024-03191-1
Figure Lengend Snippet: A FPKM values evaluated by RNA-seq for Pdcd1 (PD-1; left) and Cd38 (CD38; right) of mouse CD8 + T cells treated ± 5 mM MMA for 3 days (n = 3). B FPKM values evaluated by RNA-seq for Havcr2 (TIM-3; left) and Lag3 (LAG-3; right) of mouse CD8 + T cells treated ± 5 mM MMA for 3 days (n = 3). C MFI of PD-1 (n = 11; left) and CD38 (n = 3; right) in mouse CD8 + T cells treated ± 5 mM MMA for 3 days. D MFI of TIM-3 (left) and LAG-3 (right) in mouse CD8 + T cells treated ± 5 mM MMA for 3 days (n = 3). E Schematic representation of the proposed model by which MMA induces TOX to promote expression of exhaustion genes in CD8 + T cells. F FPKM values evaluated by RNA-seq for Tox of mouse CD8 + T cells treated ± 5 mM MMA for 3 days (n = 3). G Tox mRNA levels evaluated by RT-qPCR analysis of mouse CD8 + T cells treated ± 5 mM MMA for 3 days (n = 3). H Percentage and I MFI of TOX + splenic CD8 + T cells collected from mice administered MMA as shown in Fig. 1G (n = 8; unpaired t-test). J FPKM values evaluated by RNA-seq for Cxcr5 (CXCR5; left), Slamf6 (SLAMF6; middle), and Tcf7 (TCF-1; right) of mouse CD8 + T cells treated ± 5 mM MMA for 3 days (n = 3). K FPKM values evaluated by RNA-seq for Entpd1 (CD39) of mouse CD8 + T cells treated ± 5 mM MMA for 3 days (n = 3). L MFI of PD-1 in mouse CD8 + T cells treated with the indicated concentrations of MMA for 3 days (n = 6; repeated measures one-way ANOVA). M Fold change of live cell numbers of mouse CD8 + T cells treated with vehicle, 5 mM MMA, 1x nucleosides, or combination of MMA and nucleosides for 3 days (n = 8; one-way ANOVA). N Cell cycle progression of mouse CD8 + T cells treated with vehicle, 5 mM MMA, 1x nucleosides, or combination of MMA and nucleosides for 3 days (n = 8; two-way ANOVA). O Fold change of CD25 MFI and P PD-1 MFI of mouse CD8 + T cells treated with vehicle, 5 mM MMA, 1x nucleosides, or combination of MMA and nucleosides for 3 days (n = 7; one-way ANOVA). Data are represented as the mean ± SEM with statistical significance measured by paired t-tests unless otherwise indicated. Each dot represents an independent replicate.
Article Snippet: At endpoint, propidium iodide (Sigma-Aldrich) was used to assess tumor cell death using Incucyte S3 Live-Cell Analysis System v2021A (Sartorius, Göttingen, Germany).
Techniques: RNA Sequencing, Expressing, Quantitative RT-PCR
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