FIGURE 7 from CAR T-cell Design-dependent Remodeling of the Brain Tumor Immune Microenvironment Modulates Tumor-associated Macrophages and Anti-glioma Activity
Year: 2023
Type: other
Abstract: Global Mac/MG depletion abrogates effective CAR T-cell responses. GL261 glioma-bearing mice were treated with BLZ945 at 200 mg/kg starting 5 days after tumor implantation. A, Experimental scheme of BLZ945 macrophage depletion kinetics experiment. Daily drug dosing via oral gavage was for 2 weeks and tumors were harvested for FACS analysis at days 9, 16, and 20 after tumor implantation. B, Summary plot showing frequency of TAMs infiltrating tumors as percentage of live CD45+ immune cells. C, Experimental scheme for combination study. Glioma-bearing mice were treated with BLZ945 at 200 mg/kg starting 5 days after tumor implantation and continued daily for 3 weeks. B7-H3 CAR T-cells with Ctrl or 28.mζ constructs were then injected intratumorally at day 16. D, Kaplan–Meier survival curve (n = 11, log-rank Mantel–Cox test with Bonferroni correction for multiple comparisons, ***, P < 0.001). E, Representative images from immunostaining for T-cell and macrophage markers from tumors at endpoint showing CD3 and Iba1 staining in brain samples from each treatment group at 40x magnification (scale bar = 100 µm). F, H-scores depicting quantitative analysis of CD3 and Iba1 staining in brain tumor samples at endpoint from E as evaluated by blinded pathologist.
Authors: Dalia Haydar, Jorge Ibañez-Vega, Jeremy Chase Crawford, Ching-Heng Chou, Clifford S. Guy, Michaela Meehl, Zhongzhen Yi, Scott Perry, Jonathan Laxton, Trevor Cunningham, Deanna Langfitt, Peter Vogel, Christopher DeRenzo, Stephen Gottschalk, Martine F. Roussel, Paul G. Thomas, Giedre Krenciute
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W4389209394