Abstract B123: Oncostatin M receptor (OSMR) is a tumor-selective target in pancreatic ductal adenocarcinoma: Quantitative expression in primary and metastatic patient tumors
Naveenkumar Chandrashekhar, Edward Opichka, Kshitij S. Gaur, Gabrielle Scheuber, Baomou Feng, Anjali Geethadevi, Ishaque P. Kadamberi, Jason Yuan, Jenny Grewal, Mohammed Aldakkak, Mandana Kamgar, Thomas McFall, Nikki Lytle, Douglas B. Evans, Pradeep Chaluvally, Yongwoo D. SeoAbstract
Background:
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with limited therapeutic options and few validated tumor-selective surface targets. The Oncostatin M receptor (OSMR), an IL-6–family cytokine receptor, is expressed on PDAC tumor cells and cancer-associated fibroblasts, while its ligand, Oncostatin M (OSM), is produced predominantly by tumor-associated macrophages, establishing a pro-tumorigenic signaling axis. Elevated OSMR and OSM expression is strongly associated with adverse outcomes across solid tumors and is particularly prognostic in PDAC. However, the magnitude and cellular localization of OSMR expression in primary and metastatic human PDAC, relative to adjacent normal tissue, have not been rigorously quantified.
Methods:
OSMR and EpCAM expression were quantified by immunohistochemistry (IHC) with digital image analysis in patient-matched PDAC and liver-metastasis specimens obtained through our Surgical Oncology Tissue Bank, comparing tumor regions with adjacent normal tissue. EpCAM co-staining was used to define malignant epithelium and distinguish tumor cells from surrounding stroma. In parallel, patient-derived organotypic tumor slice cultures were generated from fresh PDAC surgical resections and tissue viability was monitored over 72 hours by MTS assay, establishing a primary-tissue platform that preserves the native tumor microenvironment.
Results:
Quantitative IHC demonstrated tumor-selective OSMR expression. OSMR was positive in 90% of PDAC tumor cells and 73% of matched liver-metastasis tumor cells, versus 42% and 4% of adjacent-normal cells, respectively. Staining was cytoplasmic and membranous and co-registered with EpCAM-positive malignant epithelium, confirming localization to tumor cells rather than surrounding stroma, and demonstrating that OSMR overexpression is retained in metastatic disease. Patient-derived organotypic slice cultures from fresh PDAC resections maintained tissue viability over 72 hours in culture, providing a tractable primary human platform in which OSMR-directed strategies can be evaluated.
Conclusions:
OSMR is highly and selectively expressed by PDAC tumor cells in both primary and metastatic disease, with markedly lower expression in adjacent normal tissue—a differential that suggests a potential therapeutic window. These findings nominate OSMR as a valuable and biologically compelling target for further exploration in pancreatic cancer, including evaluation with OSMR-directed targeted agents or antibody–drug conjugates. Ongoing studies expanding specimen numbers, quantifying OSMR across KRAS-mutant backgrounds, and leveraging patient-derived organotypic cultures will define the therapeutic potential of targeting this axis.
Citation Format:
Naveenkumar Chandrashekhar, Edward Opichka, Kshitij S. Gaur, Gabrielle Scheuber, Baomou Feng, Anjali Geethadevi, Ishaque P. Kadamberi, Jason Yuan, Jenny Grewal, Mohammed Aldakkak, Mandana Kamgar, Thomas McFall, Nikki Lytle, Douglas B. Evans, Pradeep Chaluvally, Yongwoo D. Seo. Oncostatin M receptor (OSMR) is a tumor-selective target in pancreatic ductal adenocarcinoma: Quantitative expression in primary and metastatic patient tumors [abstract]. In: Proceedings of the AACR Conference on Pancreatic Cancer: New Frontiers in Biology and Therapeutic Development; 2026 Sep 25-28; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(18_Suppl_2):Abstract nr B123.