Untangling the complexity of programmed death-ligand 1 (PD-L1) expression within a heterogeneous tumor microenvironment is an urgent challenge in PD-1/PD-L1 immune checkpoint blockade therapy. Here, we address this challenge with a method, termed transparent tumor tomography (T3), facilitating three-dimensional (3D) visualization and spatial analysis of distributions of multiple biomarkers including Her2, CD45, Ki-67, CD31, and PD-L1 throughout transgenic mouse mammary tumors. Based on our T3 imaging, we reveal that PD-L1 expression within the tumor microenvironment is highly adaptable to tumor status for efficiently preventing immune cell infiltration into the tumor. We also determine spatial pharmacokinetics of anti-PD-L1 antibody in the whole mouse mammary tumor in the context of hypoxia, CD31+ blood vessels, and target PD-L1+ cells. Finally, we demonstrate broad distribution of tumor infiltrating CD3+CD8+ cytotoxic T cells following radiation and anti-PD-L1 antibody therapy. These results provide unique spatial insights into PD-L1 cloaking and PD-L1 blockade therapy.
Citation Format: Steve Seung-Young Lee. Transparent tumor tomography (T3): Spatial analysis for PD-L1 checkpoint blockade immunotherapy [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr B084.
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