Ultrasound Imaging of Tumor Vascular CD93 with MMRN2 Modified Microbubbles for Immune Microenvironment Prediction

Vascular microenvironment is found to be closely related to immunotherapy efficacy. Identification and ultrasound imaging of the unique vascular characteristics able to predict immune microenvironment are important for immunotherapy decision-making. Herein, it is proved that high CD93 expression in the tumor vessels is closely related to the poor immune response of prostate Cancer. For ultrasound molecular imaging of CD93, CD93-targeted microbubbles (MBs) consisted of a gaseous core and the MMRN2 (Multimerin-2) containing cell membrane/lipid hybrid membrane are then synthesized. In vitro and in vivo assays demonstrate that these MBs can recognize CD93 efficiently and then accumulate within tumor regions highly expressing CD93. Contrast-enhanced ultrasound imaging with CD93-targeted MBs demonstrates that ultrasound intensity is negatively related with inflammatory tumor immune microenvironment and cytotoxic T cell infiltration. Together, endothelial expression of CD93 in tumor is a unique predictor of immunosuppressive microenvironment and CD93-targeted MBs have a great potential of evaluating tumor immune status. This article is protected by copyright. All rights reserved.

CD93; tumor immune microenvironment; ultrasound molecular imaging; vascular normalization.