Perturbing the function of the OSM-OSMR axis in the pancreatic ductal adenocarcinoma (PDA) immune microenvironment (IME) 2175
Year: 2025
Type: article
Abstract: Description Pancreatic ductal adenocarcinoma (PDA) is a highly lethal cancer with a low survival rate and significant global mortality impact, having only a 13% 5-year relative survival rate in the US for all stages combined. The interaction between the immunosuppressive tumor microenvironment (TME) in PDA, characterized by limited CD8+ T cell infiltration and an imbalance of cytokines, underscores the need to explore mechanisms underlying the inhibitory immune microenvironment (IME) to improve immunotherapies and adjuvant treatments. Intercellular crosstalk within the PDA TME, driven by secreted proteins, cytokines, chemokines, and their receptors, plays a critical role in maintaining immunosuppression. Our studies highlight Oncostatin M (OSM) and its receptor OSMR as potential regulators of the IME, promoting its shift from “hot” to “cold.” Spatial transcriptomics reveals OSM expression in tumor-associated macrophages (TAM) and OSMR on cancer-associated fibroblasts (CAFs) and PDA cells, which may sustain an immune-suppressive IME, marked by immunosuppressive macrophages and fewer cytotoxic T cells. Monocytes cocultured with PDA tumor cells exhibit enhanced OSM-OSMR responses, affecting macrophage activity. Blocking OSM-OSMR signaling could disrupt this suppression, enhancing immunotherapy effectiveness. We aim to elucidate this immune switch mechanism and test OSM-OSMR blockade in the KPC mouse PDA model to support its potential as a novel adjuvant PDA therapy. Funding Sources This work was in part funded by NIH-P01 (CA265762 Project 2), NIH-R35 (CA242443), a Lustgarden Award for Pancreatic Research, and the NOMIS fundation. Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)
Source: The Journal of Immunology
Authors: Yuan Sui, Tony Hunter
Institution: Salk Institute for Biological Studies
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4416446159
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