University of Wisconsin Carbone Cancer Center

Direct physical contacts with epithelial cells regulate leukocyte actin dynamics to facilitate intraepithelial motility in vivo

Efficient immune cell migration requires physical interactions with surrounding tissues. While tissue matrix mechanics influence leukocyte motility, it is unknown how leukocytes exert pushing and pulling forces to traverse cell-dense epithelial tissues in vivo. Here, we leverage...

Intratumoral Immunotherapy—The Future of Treating Merkel Cell Carcinoma?

Merkel cell carcinoma (MCC) represents a rare but highly aggressive neuroendocrine skin cancer with limited systemic therapy options for patients who fail or are ineligible for immune checkpoint inhibitors (ICIs). Intratumoral (IT) immunotherapy has emerged as a promising strateg...

In Situ detection of protein-phosphoinositide signalosome in tissues by immunohistochemistry-coupled proximity ligation assay

Abstract Phosphoinositides (PIPs) are central lipid signaling molecules, with PtdIns(3,4,5)P 3 acting as a key regulator of the PI3K-AKT pathway and a major driver of tumorigenesis. Together with p53 mutations or loss, this pathway represents one of the most frequently dysregulat...

A CD40-Targeted IL-21 fusokine enables rapid generation of human IL-10⁺granzyme B⁺ regulatory B cells

Regulatory B cells (Bregs) suppress pathogenic immune responses and maintain immune homeostasis, but their rarity and poor ex vivo expandability limit clinical translation as cellular therapeutics. Here, we describe a feeder-free platform for rapid generation of human IL-10⁺Granz...

Prioritizing clinical utility to use allostatic load as a biomarker of the consequences of stress

Allostatic load measures the physiological consequences of stress and is associated with disease outcomes. Clinical use of allostatic load is limited, in part, because its calculation requires biomarkers not routinely measured in clinical care. Presently, we evaluated association...

Lymphatic endothelial cells regulate neutrophil phenotypes and function in a microphysiological model of infection

Early skin inflammation requires coordinated immune regulation, with neutrophils acting as first-line responders. While the blood vasculature and its role in neutrophil recruitment during infection has been extensively studied, the lymphatic system remains comparatively understud...