title: Lung cancer-derived galectin-1 mediates dendritic cell anergy through inhibitor of DNA binding 3/IL-10 signaling pathway.
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.
authors.affiliation: Institute of Clinical Medicine, Kaohsiung Medical University, 807 Kaohsiung, Taiwan.
authors.forename: Po-Lin
authors.initials: PL
authors.lastname: Kuo
authors.forename: Jen-Yu
authors.initials: JY
authors.lastname: Hung
authors.forename: Shau-Ku
authors.initials: SK
authors.lastname: Huang
authors.forename: Shah-Hwa
authors.initials: SH
authors.lastname: Chou
authors.forename: Da-En
authors.initials: DE
authors.lastname: Cheng
authors.forename: Yuh-Jyh
authors.initials: YJ
authors.lastname: Jong
authors.forename: Chih-Hsing
authors.initials: CH
authors.lastname: Hung
authors.forename: Chih-Jen
authors.initials: CJ
authors.lastname: Yang
authors.forename: Ying-Ming
authors.initials: YM
authors.lastname: Tsai
authors.forename: Ya-Ling
authors.initials: YL
authors.lastname: Hsu
authors.forename: Ming-Shyan
authors.initials: MS
authors.lastname: Huang
mesh_terms: D000818:Animals; D001980:Bronchi / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018827:Carcinoma, Lewis Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D017635:Clonal Anergy / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D037483:Galectin 1 / Q000502:physiology*; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods; D051796:Inhibitor of Differentiation Proteins / Q000096:biosynthesis / Q000502:physiology*; D016753:Interleukin-10 / Q000096:biosynthesis / Q000502:physiology*; D008175:Lung Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000502:physiology*; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000276:immunology*
chemical_list: D037483:Galectin 1; D051796:Inhibitor of Differentiation Proteins; D009363:Neoplasm Proteins; D016753:Interleukin-10; C075640:ID3 protein, human