Secretory Nogo-B regulates Th2 differentiation in the lung cancer microenvironment

•Nogo-B is highly secreted by lung cancer cells.•The concentration of Nogo-B in the serum of lung cancer patients was significantly elevated and showed a significant positive correlation with tumor size.•ER stress and phosphorylation at S107 promote the secretion of Nogo-B in lung cancer cells.•Secr...

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Bibliographic Details
Published in:International immunopharmacology 2024-10, Vol.140, p.112763, Article 112763
Main Authors: Qin, Changfei, Li, Wenxia, Zhang, Yi, Wang, Zhaojun, Leng, Yang, Ma, Jingyun, Qin, Chao, Cheng, Shumin, Xue, Ling, Song, Kuangyu, Huang, Bihui
Format: Article
Language:English
Subjects:
Cell Differentiation
Cell Line, Tumor
Cytokines - metabolism
Endoplasmic reticulum stress
Endoplasmic Reticulum Stress - immunology
Female
Humans
Lung cancer
Lung Neoplasms - genetics
Lung Neoplasms - immunology
Lung Neoplasms - metabolism
Lung Neoplasms - pathology
Male
Nogo Proteins - genetics
Nogo Proteins - metabolism
Nogo-B
Phosphorylation
Secretion
Th2 cell
Th2 Cells - immunology
Tumor Microenvironment - immunology
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Summary:•Nogo-B is highly secreted by lung cancer cells.•The concentration of Nogo-B in the serum of lung cancer patients was significantly elevated and showed a significant positive correlation with tumor size.•ER stress and phosphorylation at S107 promote the secretion of Nogo-B in lung cancer cells.•Secretory Nogo-B may reshape the tumor immune microenvironment and promote tumor progression by inhibiting the function of tumor-infiltrating immune cells, especially Th2 cells. Nogo-B, a ubiquitously expressed member of the reticulon family, plays an important role in maintaining endoplasmic reticulum (ER) structure, regulating protein folding, and calcium homeostasis. In this study, we demonstrate that Nogo-B expression and secretion are upregulated in lung cancer and correlate to overall survival. Nogo-B is secreted by various cells, particularly lung cancer cells. ER stress and phosphorylation at serine 107 can induce Nogo-B secretion. Secretory Nogo-B suppresses the differentiation of Th2 cells and the release of type 2 cytokines, thus influencing the anti-tumor effects of Th2-related immune cells, including IgE+B cell class switching and eosinophil activation.
ISSN:1567-5769
1878-1705
1878-1705
DOI:10.1016/j.intimp.2024.112763