Figure 4 from Metabolic Reprogramming of Tumor-Associated Macrophages Using Glutamine Antagonist JHU083 Drives Tumor Immunity in Myeloid-Rich Prostate and Bladder Cancers
Year: 2024
Type: other
Abstract: JHU083-induced glutamine antagonism caused a divergent metabolic response affecting glycolysis, purine metabolism, and succinate in TAMs. A and B, Surface and intracellular expression of GLUT1 and HKII (percentage positive population and mean fluorescence intensity) on B6CaP-derived TAMs. C, GSEA showing the enrichment of the Hallmark glycolysis gene set among DEGs in bulk RNA-sequenced FACS-sorted B6CaP-derived TAMs following JHU083 treatment relative to control. D, Heat map showing the differential metabolites in TAMs sorted from JHU083-treated and control B6CaP tumors (n = 3/group). E, Volcano plot showing log2 fold change vs. –log10 (FDR-corrected P value), representing fold changes in metabolite abundance in one-carbon metabolism, purine nucleotide metabolism, and hexosamine pathway in JHU083-treated vs. control TAMs. F, Normalized relative labeled metabolites from U-13C glucose in the TCA cycle in TAMs derived from B6CaP tumors (n = 9/group in two independent experiments). G, Normalized relative metabolite abundances in the TCA cycle in TAMs derived from B6CaP tumors (n = 9/group from two independent experiments) and (H) log fold-change of TCA cycle enzymes and inflammatory cytokine transcripts in TAMs (from scRNA-seq at an early time point (day 7 posttreatment). DEGs for GSEA in C were calculated with DESeq2, and statistics on genes of interest in H were calculated with the Wilcoxon rank-sum test. All other statistical analyses were performed using the unpaired t test (*, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001).
Authors: Monali Praharaj, Fan Shen, Alex J. Lee, Liang Zhao, Thomas R. Nirschl, Debebe Theodros, Alok K. Singh, Xiaoxu Wang, Kenneth M. Adusei, Kara A. Lombardo, Raekwon A. Williams, Laura A. Sena, Elizabeth A. Thompson, Ada Tam, Srinivasan Yegnasubramanian, Edward J. Pearce, Robert D. Leone, Jesse Alt, Rana Rais, Barbara S. Slusher, Drew M. Pardoll, Jonathan D. Powell, Jelani C. Zarif
Language: English
Topic: Immune cells in cancer
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
OpenAlex ID: W4400244358