Lung cancer-derived galectin-1 mediates dendritic cell anergy through inhibitor of DNA binding 3/IL-10 signaling pathway

Po Lin Kuo, Jen Yu Hung, Shau Ku Huang, Shah Hwa Chou, Da En Cheng, Yuh Jyh Jong, Chih Hsing Hung, Chih Jen Yang, Ying Ming Tsai, Ya Ling Hsu, Ming Shyan Huang

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Lung cancer, one of the leading causes of death worldwide, is often associated with a state of immune suppression, but the molecular and functional basis remains enigmatic. Evidence is provided in this paper supporting the role of lung cancer-derived soluble lectin, galectin-1, as a culprit in dendritic cell (DC) anergy. We have shown that galectin-1 is highly expressed in lung cancer cell lines, together with the serum and surgical samples from lung cancer patients. Functionally, lung cancer-derived galectin-1 has been shown to alter the phenotypes of monocyte-derived DCs (MdDCs) and impair alloreactive T cell response, concomitant with the increase of CD4+CD25 +FOXP3+ regulatory T cells. The regulatory effect of galectin-1 is mediated, in part, through its ability to induce, in an Id3 (inhibitor of DNA binding 3)-dependent manner, the expression of IL-10 in monocytes and MdDCs. This effect is inhibited by the addition of lactose, which normalizes the phenotypic and functional alterations seen in MdDCs. Of note, significant upregulation of IL-10 was seen in tumor-infiltrating CD11c + DCs in human lung cancer samples. This was also noted in mice transplanted with lung cancer cells, but not in those receiving tumor cells with galectin-1 knockdown. Furthermore, a significant reduction was noted in lung cancer incidence and in the levels of IL-10-expressing, tumor-infiltrating DCs, in mice receiving galectin-1-silenced tumor cells. These results thus suggest that the galectin-1/IL-10 functional axis may be crucial in lung cancer-mediated immune suppression, and that galectin-1 may serve as a target in the development of lung cancer immunotherapy.

Original languageEnglish
Pages (from-to)1521-1530
Number of pages10
JournalJournal of Immunology
Volume186
Issue number3
DOIs
Publication statusPublished - Feb 1 2011
Externally publishedYes

    Fingerprint

ASJC Scopus subject areas

  • Immunology

Cite this

Kuo, P. L., Hung, J. Y., Huang, S. K., Chou, S. H., Cheng, D. E., Jong, Y. J., Hung, C. H., Yang, C. J., Tsai, Y. M., Hsu, Y. L., & Huang, M. S. (2011). Lung cancer-derived galectin-1 mediates dendritic cell anergy through inhibitor of DNA binding 3/IL-10 signaling pathway. Journal of Immunology, 186(3), 1521-1530. https://doi.org/10.4049/jimmunol.1002940