Endothelin B receptor mediates the endothelial barrier to T cell homing to tumors and disables immune therapy

Author & Article Information Authors: Ronald J Buckanovich, Andrea Facciabene, Sarah Kim, Fabian Benencia, Dimitra Sasaroli, Klara Balint, Dionysios Katsaros, Anne O'Brien-Jenkins, Phyllis A Gimotty & George Coukos Nature Medicine volume 14 , pages28–36 Abstract In spite of their having sufficient immunogenicity, tumor vaccines remain largely ineffective. The mechanisms underlying this lack of efficacy are still unclear. Here we report a previously undescribed mechanism by which the tumor endothelium prevents T cell homing and hinders tumor immunotherapy. Transcriptional profiling of microdissected tumor endothelial cells from human ovarian cancers revealed genes associated with the absence or presence of tumor-infiltrating lymphocytes (TILs). Overexpression of the endothelin B receptor (ETBR) was associated with the absence of TILs and short patient survival time. The ETBR inhibitor BQ-788 increased T cell adhesion to human endothelium in vitro , an effect countered by intercellular adhesion molecule-1 (ICAM-1) blockade or treatment with NO donors. In mice, ETBR neutralization by BQ-788 increased T cell homing to tumors; this homing required ICAM-1 and enabled tumor response to otherwise ineffective immunotherapy in vivo without changes in systemic antitumor immune response. These findings highlight a molecular mechanism with the potential to be pharmacologically manipulated to enhance the efficacy of tumor immunotherapy in humans. Read More See the original article here | Nature Medicine Endothelin B receptor and tumor immunity T cell homing blockade in cancer Tumor endothelium and immune evasion ICAM-1 and cancer immunotherapy Enhancing TIL infiltration in tumors Rob Bent Previous Previous Intercellular adhesion molecule-1-dependent stable interactions between T cells and dendritic cells determine CD8+ T cell memory Next Next Tumor blood vessels, a difficult hurdle for infiltrating leukocytes 2450 Holcombe Blvd, Suite J Houston, TX 77021 [email protected] © 2025. 7 Hills Pharma Inc. Menu Home About Leadership Technology News & Publications Contact Newsletter Block This newsletter signup form needs a storage option. Edit the block and enter a storage location via the Storage tab. Subscribe Sign up with your email address to receive news and updates. Email Address Sign Up We respect your privacy. Thank you!

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