Publications by authors named "Joshua Wiesner"
Stimulatory type 1 conventional dendritic cells (cDC1s) engage in productive interactions with CD8 effectors along tumor-stroma boundaries. The paradoxical accumulation of "poised" cDC1s within stromal sheets is unlikely to simply reflect passive exclusion from tumor cores. Drawing parallels with embryonic morphogenesis, we hypothesized that invasive margin stromal remodeling generates developmentally conserved cell fate cues that regulate cDC1 behavior.
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- Multiple myeloma (MM) is a type of cancer that affects plasma cells, and it's often resistant to common treatments, especially in advanced stages with genetic mutations in the RAS pathway.
- Researchers developed a mouse model called VQ MM to study this advanced form and screened 147 FDA-approved anti-cancer drugs, finding that the combination of trametinib (Tra) and ponatinib (Pon) was particularly effective, prolonging survival in mice.
- However, ponatinib negatively impacted the function of CD8 T cells, which are important for immune response, suggesting that while it enhances treatment effects, it may also reduce immune response, highlighting the need for balanced therapy approaches.
Versican is an extracellular matrix proteoglycan with key roles in multiple facets of cancer development, ranging from proliferative signaling, evasion of growth-suppressor pathways, regulation of cell death, promotion of neoangiogenesis, and tissue invasion and metastasis. Multiple lines of evidence implicate versican and its bioactive proteolytic fragments (matrikines) in the regulation of cancer inflammation and antitumor immune responses. The understanding of the dynamics of versican deposition/accumulation and its proteolytic turnover holds potential for the development of novel immune biomarkers as well as approaches to reset the immune thermostat of tumors, thus promoting efficacy of modern immunotherapies.
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