Immune modulation in cholangiocarcinoma through targeted Sulfatase-2 Inhibition for therapeutic intervention 4711
Year: 2025
Type: article
Abstract: Description Cholangiocarcinoma (CCA) is an aggressive epithelial malignancy of the bile duct, with rising global incidence and poor prognosis. Current treatments achieve only 20-30% response rates in advanced cases, highlighting the need for novel therapeutic approaches. The tumor microenvironment (TME) has emerged as a critical focus for innovative therapies. Sulfatase 2 (SULF2) is a heparan sulfate (HS)-editing enzyme that alters HS chain affinity for growth factors and receptors, modulating heparan sulfate proteoglycans (HSPG) in cell signaling pathways. Specific sulfatases in HSPGs have been implicated as therapeutic targets in CCA. This study investigates the potential of anti-SULF2 antibodies to modulate immune cells within the TME using a C57BL6 syngeneic mouse model. Anti-SULF2-treated mice were compared to untreated controls, with tumors analyzed via CyTOF. Treatment resulted in reduced immunosuppressive cells and increased anti-tumor immune cells, suggesting that SULF2 inhibition shifts the TME toward an anti-tumorigenic state. These findings highlight SULF2 as a promising target for therapeutic intervention. Future studies will explore spatial transcriptomic and proteomics to elucidate the interplay between SULF2 expression in the TME makeup. We will also explore the molecular mechanisms of SULF2 suppression and its influence on cytokine signaling pathways within the TME. Funding Sources Supported by CTSA Grant Number TL1 TR002380 from the National Center for Advancing Translational Science (NCATS). Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)
Source: The Journal of Immunology
Institutions: Mayo Clinic, Mayo Clinic in Arizona
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4416448247
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