Allison Bontrager
Pronouns: she/her
Research Mentor(s): Anutosh Ganguly
Research Mentor School/College/Department: Surgery / Medicine
Program:
Authors:
Session: Session 6: 3:40 pm – 4:30 pm
Poster: 10
Abstract
Preclinical studies from our laboratory have shown that tumor treatment with histotripsy, a non-invasive ablation modality that uses focused ultrasound pulses to induce mechanical disruption of cellular and subcellular structures, triggers an array of physiological changes within the tumor microenvironment that may be conducive to oncological therapy. Previous studies from our laboratory have shown that histotripsy triggers immunogenic cell death of cancer cells followed by innate and adaptive immune cell activation, culminating in the influx of tumor-specific cytotoxic T cells into local and distant tumors. In this study, we have found histotripsy treatment causes rapid changes in vascular anatomy that are accompanied by marked reversal of intratumoral hypoxia and enhanced uptake of intravenously-administered drugs. Heterotopic pancreatic adenocarcinoma (mT4) and orthotopic flank melanoma (B16F10) bearing mice were subjected to either sham therapy or histotripsy to 70% of the target tumor volume. A week after the treatment, doxorubicin, a chemotherapeutic drug that has intrinsic fluorescent property was injected into the tail vein of the mice, and drug delivery was quantitated with spectral imaging, using a confocal microscope. The tumors of the mice in the histotripsy treated group were found to have increased drug permeability into the tumor as seen by increased doxorubicin delivery as compared to the sham therapy group. By histopathology, at the molecular level we observe a significant increase in intratumoral blood vessel diameter and a decrease in intratumoral blood vessel branching. Manifestations of angiogenesis including number of vascular nodes, total vessel length, and length of vasculature branches, are significantly reduced following histotripsy. These data strongly indicate that histotripsy induces vascular normalization of the tumor microenvironment, which is a process of blood vessel remodeling that favors tumor oxygenation and drug delivery.
