Sefton, J. | Search bioRxiv

bioRxiv2024

Craters on the melanoma surface facilitate tumor-immune interactions and demonstrate pathologic response to checkpoint blockade in humans

Immunotherapy leads to cancer eradication despite the tumors immunosuppressive environment. Here, we used extended long-term in-vivo imaging and high-resolution spatial transcriptomics of endogenous melanoma in zebrafish, and multiplex imaging of human melanoma, to identify domains that facilitate immune response during immunotherapy. We identified crater-shaped pockets at the margins of zebrafish and human melanoma, rich with beta-2 microglobulin (B2M) and antigen recognition molecules. The craters harbor the highest density of CD8+ T cells in the tumor. In zebrafish, CD8+ T cells formed prolonged interactions with melanoma cells within craters, characteristic of antigen recognition. Following immunostimulatory treatment, the craters enlarged and became the major site of activated CD8+ T cell accumulation and tumor killing that was B2M dependent. In humans, craters predicted immune response to ICB therapy, showing response better than high T cell infiltration. This marks craters as potential new diagnostic tool for immunotherapy success and targets to enhance ICB response.

cancer biology↗

bioRxiv2023

Myofascial Trigger Point (MTrP) Size and Elasticity Properties Can Be Used to Differentiate Active and Latent MTrPs in Lower Back Skeletal Muscle

Myofascial Trigger Points (MTrPs) are localized contraction knots that develop after muscle overuse or an acute trauma. Significant work has been done to understand, diagnose, and treat MTrPs in order to improve patients suffering from their effects. However, effective non-invasive diagnostic tools are still a missing gap in both understanding and treating MTrPs. Effective treatments for patients suffering from MTrP mediated pain require a means to measure MTrP properties quantitatively and diagnostically both prior to and during intervention. Further, quantitative measurements of MTrPs are often limited by the availability of equipment and training. Here we develop ultrasound (US) based diagnostic metrics that clinicians can use during patient diagnosis and treatment. We highlight the advantages and limitations of previous US-based approaches that utilize elasticity theory. We show how US-based measurements can distinguish Active from Latent MTrPs. We demonstrate that Active MTrPs tend to be smaller, stiffer, and deeper in the muscle tissue. We provide evidence that more than one MTrP within a single US-image field increases the stiffness of neighboring MTrPs. Finally, we highlight a combination of metrics (depth, thickness, and stiffness) that can be used to assess individual MTrPs in combination with standard clinical assessments.

biophysics↗