Figure 1 from Metabolic Reprogramming of Tumor-Associated Macrophages Using Glutamine Antagonist JHU083 Drives Tumor Immunity in Myeloid-Rich Prostate and Bladder Cancers

&lt;p&gt;The antitumor activity of the glutamine antagonist JHU083 against urologic tumors is myeloid dependent. &lt;b&gt;A,&lt;/b&gt; Dot plots showing expression levels and fractional abundance of myeloid cells expressing glutamine metabolism enzymes, &lt;i&gt;GLUL,&lt;/i&gt; and &lt;i&gt;GLS&lt;/i&gt; across samples (tumor, involved, distal, and benign). &lt;b&gt;B,&lt;/b&gt; Violin plots showing the expression levels and fractional abundance of different cell types expressing &lt;i&gt;GLUL&lt;/i&gt; and &lt;i&gt;GLS&lt;/i&gt;. Data for &lt;b&gt;A&lt;/b&gt; and &lt;b&gt;B&lt;/b&gt; were generated using the previously published and publicly available scRNA-seq integrated dataset from nine metastatic prostate cancer and seven benign BM control patient samples by Kfoury and colleagues (&lt;a href="#bib41" target="_blank"&gt;41&lt;/a&gt;). &lt;b&gt;C,&lt;/b&gt; Schematic diagrams showing the heterotopic syngeneic urologic tumor (B6CaP and MB49) models and therapeutic JHU083 treatment strategy. &lt;b&gt;D&lt;/b&gt; and &lt;b&gt;E,&lt;/b&gt; Tumor volume and tumor weight measurements (post-necropsy) in the B6CaP (&lt;i&gt;n&lt;/i&gt; = 8/group) and MB49 (&lt;i&gt;n&lt;/i&gt; = 9 or 10/group) tumors. &lt;b&gt;F&lt;/b&gt; and &lt;b&gt;G,&lt;/b&gt; Effects of CD8&lt;sup&gt;+&lt;/sup&gt; T cell depletion on tumor volume and animal survival for (&lt;b&gt;F&lt;/b&gt;) MB49 (&lt;i&gt;n&lt;/i&gt; = 4–5/group) and (&lt;b&gt;G&lt;/b&gt;) B6CaP (&lt;i&gt;n&lt;/i&gt; = 4–6/group) tumors, respectively. &lt;b&gt;H&lt;/b&gt; and &lt;b&gt;I,&lt;/b&gt; Effect of CD4&lt;sup&gt;+&lt;/sup&gt; T cell depletion on tumor volume of (&lt;b&gt;H&lt;/b&gt;) MB49 (&lt;i&gt;n&lt;/i&gt; = 4–5/group) and (&lt;b&gt;I&lt;/b&gt;) B6CaP (&lt;i&gt;n&lt;/i&gt; = 3–5/group) tumors and animal survival. Antitumor activity of JHU083-reprogrammed and adoptively transferred (&lt;b&gt;J)&lt;/b&gt; TAMs (CD45&lt;sup&gt;+&lt;/sup&gt; Ly6G&lt;sup&gt;−&lt;/sup&gt; CD3&lt;sup&gt;−&lt;/sup&gt; CD11b&lt;sup&gt;+&lt;/sup&gt; F4.80&lt;sup&gt;+&lt;/sup&gt;; &lt;i&gt;n&lt;/i&gt; = 5 or 10/group) and (&lt;b&gt;K&lt;/b&gt;) TIMs (CD45&lt;sup&gt;+&lt;/sup&gt; Ly6G&lt;sup&gt;−&lt;/sup&gt; CD3&lt;sup&gt;−&lt;/sup&gt; Ly6C &lt;sup&gt;(hi)&lt;/sup&gt;; &lt;i&gt;n&lt;/i&gt; = 4 or 7/group) on MB49 tumor volume (&lt;b&gt;L&lt;/b&gt;). Briefly, live, FACS-sorted TAMs or TIMs were mixed in a 1:1 ratio with cultured MB49 cells and were subsequently implanted on flanks to generate tumors in recipient mice. Data are represented as mean values ± SEM. All experiments were independently validated, at least in two separate biological replicates. Statistical analyses were performed using either &lt;i&gt;t&lt;/i&gt; test or a two-way ANOVA using Bonferroni’s multiple comparisons (*, &lt;i&gt;P&lt;/i&gt; &lt; 0.05; **, &lt;i&gt;P&lt;/i&gt; &lt; 0.01; ***, &lt;i&gt;P&lt;/i&gt; &lt; 0.001; ****, &lt;i&gt;P&lt;/i&gt; &lt; 0.0001). Log-rank (Mantel–Cox) tests were performed for survival analysis (&lt;b&gt;F,&lt;/b&gt; JHU083 relative to control, &lt;i&gt;P&lt;/i&gt; = 0.0412; α-CD8b relative to α-CD8b + JHU083, &lt;i&gt;P&lt;/i&gt; = 0.0342; α-CD8b + JHU083 vs. JHU083, &lt;i&gt;P&lt;/i&gt; = ns. &lt;b&gt;I,&lt;/b&gt; JHU083 vs. control, &lt;i&gt;P&lt;/i&gt; = 0.01; α-CD4 vs. α-CD4 + JHU083, &lt;i&gt;P&lt;/i&gt; = 0.0801; α-CD4 + JHU083 vs. JHU083, &lt;i&gt;P&lt;/i&gt; = ns).&lt;/p&gt;

Topic: Immune cells in cancer
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences