Publication: INHIBITION PROPERTIES OF GELDANAMYCIN TOWARDS LYMPHOCYTE SUPPRESSION ABILITY OF METASTATIC PANCREATIC CANCER CELLS
Date
2025
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Publisher
IMU University
Abstract
Pancreatic cancer is characterized by its aggressive metastasis and immunosuppressive microenvironment, contributing to poor therapeutic outcomes. Current strategies have had limited success, with a 5-year survival rate remaining dismal. Recent research has focused on repurposed drugs, such as geldanamycin, which has demonstrated the ability to downregulate TGFBI and C3-proteins implicated in lymphocyte suppression. However, the functional impact of this downregulation remains unclear. This study investigated whether geldanamycin modulates TGFBI and C3 to reduce lymphocyte suppression. Metastatic pancreatic cancer cell lines (PANC 10.5, SW1990) and a pancreatic stellate cell (PSC) line were treated with geldanamycin, and their conditioned medium was used to treat peripheral blood mononuclear cells. Flow cytometry analysis was used to assess the effects on lymphocyte populations. We used independent T-tests to measure differences between the untreated and treated groups. Statistical significance was defined as a p-value < 0.05. The results showed that Th1 populations increased significantly in PANC 10.5-treated (p < 0.010) and PSC-treated (p < 0.019) groups, indicating enhanced anti-tumor immunity. Additionally, geldanamycin treatment led to reductions in tumor-promoting immune subsets, including Th2 in PANC 10.5-treated (p < 0.009), Th17 PANC 10.5-treated (p < 0.018), and Total T-cell in PANC 10.5-treated (p < 0.001) and SW1990-treated (P < 0.008) populations. Significant changes were observed in B-cells for PANC 10.5, SW1990, and PSC with p-values from 0.004–0.006, cytotoxic T-cells in PANC 10.5 (p < 0.032), and PSC-treated (p < 0.047). Total T-cells further highlight geldanamycin’s immunomodulatory potential. These findings suggest that geldanamycin may counteract pancreatic cancer-induced immunosuppression by restoring key lymphocyte subsets, providing a foundation for future therapeutic applications. This study underscores its potential as an adjunct immunomodulatory agent in metastatic pancreatic cancer treatment.
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Keywords
Lymphocytes, Pancreatic Neoplasms, Immunosuppressive Agents, Tumor Microenvironment, Pancreatic Stellate Cells