Journal article
A common secretomic signature across epithelial cancers metastatic to the pleura supports IL-6 axis therapeutic targeting
Frontiers in immunology, v 15, 1404373
24 Jul 2024
PMID: 39114667
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Background Many cancers metastasize to the pleura, resulting in effusions that cause dyspnea and discomfort. Regardless of the tissue of origin, pleural malignancies are aggressive and uniformly fatal, with no treatment shown to prolong life. The pleural mesothelial monolayer is joined by tight junctions forming a contained bioreactor-like space, concentrating cytokines and chemokines secreted by the mesothelium, tumor, and infiltrating immune cells. This space represents a unique environment that profoundly influences tumor and immune cell behavior. Defining the pleural secretome is an important step in the rational development localized intrapleural immunotherapy.Method We measured cytokine/chemokine content of 252 malignant pleural effusion (MPE) samples across multiple cancers using a 40-analyte panel and Luminex multiplexing technology.Results Eleven analytes were consistently present in concentrations >= 10.0 pM: CXCL10/IP10 (geometric mean = 672.3 pM), CCL2/MCP1 (562.9 pM), sIL-6R alpha (403.1 pM), IL-6 (137.6 pM), CXCL1/GRO (80.3 pM), TGF beta 1 (76.8 pM), CCL22/MDC (54.8 pM), CXCL8/IL-8 (29.2 pM), CCL11/Eotaxin (12.6 pM), IL-10 (11.3 pM), and G-CSF (11.0 pM). All are capable of mediating chemotaxis, promotion of epithelial to mesenchymal transition, or immunosuppression, and many of are reportedly downstream of a pro-inflammatory cytokine cascade mediated by cytokine IL-6 and its soluble receptor.Conclusion The data indicate high concentrations of several cytokines and chemokines across epithelial cancers metastatic to the pleura and support the contention that the pleural environment is the major factor responsible for the clinical course of MPE across cancer types. A sIL-6R alpha to IL-6 molar ratio of 2.7 ensures that virtually all epithelial, immune and vascular endothelial cells in the pleural environment are affected by IL-6 signaling. The central role likely played by IL-6 in the pathogenesis of MPE argues in favor of a therapeutic approach targeting the IL-6/IL-6R axis.
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Details
- Title
- A common secretomic signature across epithelial cancers metastatic to the pleura supports IL-6 axis therapeutic targeting
- Creators
- Vera S. Donnenberg - University of PittsburghJames D. Luketich - University of PittsburghBosko Popov - UPMC Hillman Cancer CenterDavid L. Bartlett - Drexel UniversityAlbert D. Donnenberg - Allegheny Health Network
- Publication Details
- Frontiers in immunology, v 15, 1404373
- Publisher
- Frontiers Media Sa
- Number of pages
- 11
- Grant note
- METAvivor10.13039/100012639
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Surgery; General Internal Medicine
- Web of Science ID
- WOS:001284573000001
- Scopus ID
- 2-s2.0-85200678698
- Other Identifier
- 991022202123604721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Immunology