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Büchel G, Schulte JH, Harrison L, et al. Immune response modulation by Galectin-1 in a transgenic model of neuroblastoma. Oncoimmunology. 2016;5(5):e1131378doi: 10.1080/2162402X.2015.1131378.
Büchel, G., Schulte, J. H., Harrison, L., Batzke, K., Schüller, U., Hansen, W., & Schramm, A. (2016). Immune response modulation by Galectin-1 in a transgenic model of neuroblastoma. Oncoimmunology, 5(5), e1131378. https://doi.org/10.1080/2162402X.2015.1131378
Büchel, Gabriele, et al. "Immune response modulation by Galectin-1 in a transgenic model of neuroblastoma." Oncoimmunology vol. 5,5 (2016): e1131378. doi: https://doi.org/10.1080/2162402X.2015.1131378
Büchel G, Schulte JH, Harrison L, Batzke K, Schüller U, Hansen W, Schramm A. Immune response modulation by Galectin-1 in a transgenic model of neuroblastoma. Oncoimmunology. 2016 Feb 18;5(5):e1131378. doi: 10.1080/2162402X.2015.1131378. eCollection 2016 May. PMID: 27467948; PMCID: PMC4910755.
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Oncoimmunology. 2016 Feb 18;5(5):e1131378. doi: 10.1080/2162402X.2015.1131378. eCollection 2016 May.

Immune response modulation by Galectin-1 in a transgenic model of neuroblastoma.

Oncoimmunology

Gabriele Büchel, Johannes H Schulte, Luke Harrison, Katharina Batzke, Ulrich Schüller, Wiebke Hansen, Alexander Schramm

Affiliations

  1. Pediatric Oncology and Hematology, University Children's Hospital Essen, University of Duisburg-Essen , Essen, Germany.
  2. Pediatric Oncology and Hematology, Charité University Medicine , Berlin, Germany.
  3. Center for Neuropathology, Ludwig-Maximilians-University , Munich, Germany.
  4. Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen , Essen, Germany.

PMID: 27467948 PMCID: PMC4910755 DOI: 10.1080/2162402X.2015.1131378

Abstract

Galectin-1 (Gal-1) has been described to promote tumor growth by inducing angiogenesis and to contribute to tumor immune escape by promoting apoptosis of activated T cells. We had previously identified upregulation of Gal-1 in preclinical models of aggressive neuroblastoma (NB), a solid tumor of childhood. However, the clinical and biological relevance of Gal-1 in this tumor entity is unclear. Here, the effect of Gal-1 on the immune system and tumorigenesis was assessed using modulation of Gal-1 expression in immune effector cells and in a transgenic NB model, designated TH-MYCN. The fraction of CD4(+) T cells was decreased in tumor-bearing TH-MYCN mice compared to tumor-free littermates, while both CD4(+) T cells as well as CD8(+) T cells were less activated, compatible with a reduced immune response in tumor-bearing mice. Tumor incidence was not significantly altered by decreasing Gal-1/LGALS1 gene dosage in TH-MYCN mice, but TH-MYCN/Gal-1(-/-) double transgenic mice displayed impaired tumor angiogenesis, splenomegaly, and impaired T cell tumor-infiltration with no differences in T cell activation and apoptosis rate. Additionally, a lower migratory capacity of Gal-1 deficient CD4(+) T cells toward tumor cells was observed in vitro. Transplantation of TH-MYCN-derived tumor cells into syngeneic mice resulted in significantly reduced tumor growth and elevated immune cell infiltration when Gal-1 was downregulated by shRNA. We therefore conclude that T cell-derived Gal-1 mediates T cell tumor-infiltration, whereas NB-derived Gal-1 promotes tumor growth. This opposing effect of Gal-1 in NB should be considered in therapeutic targeting strategies, as currently being developed for other tumor entities.

Keywords: Galectin-1; neuroblastoma; tumor–host interaction

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