Targeted inhibition of galectin-1 gene expression in tumor cells results in heightened T cell-mediated rejection:

A potential mechanism of tumor-immune privilege

Speaker: 林子華

Commentator: 楊倍昌 老師

Time: May.19, 2004, 13:00~14:00

Place: Room 601

Abstract:

      One important aspect of tumor development is the devised strategies of cancer cells to avoid tumor-specific-immune attack. Evasion mechanisms can either be preexisting, arise through outgrowth of escape mutants, or take place during tumor sculpting action by the immune system (1). Through that FasL which is expressed by cancer cells can cause not only T cell apoptosis, but also anti-tumor effects in some contexts, it has been hypothesized that the maintenance of immune privilege in tumors relies not only on FasL itself but also on the collective production of as yet unidentified immunosuppressive factors. Galectin-1 (Gal1), which is expressed by many different tumor types, is a carbohydrate-binding protein with regulatory functions. Increased expression of Gal1 has been correlated with tumor aggressiveness and metastasis (2). In this study, the authors transfected the B16 mouse melanoma cells with Gal1 anti-sense cDNA to establish Gal1 knockdown clones. The Gal1 knockdown clones were rejected when inoculated in vivo,compared with wild-type B16 melanoma cells.  Furthermore, mice that had exposed to the Gal1 knockdown B16 cells were then able to resist subsequent challenge with wild-type B16 cells. The authors also proved that the tumor rejection requires intact CD4⁺ and CD8⁺ T cell responses, and the tumor-specific Th1-immune response can be generated by blockade of Gal1 synthesis (3). These results provide strong evidence that Gal1 contributes to immune privilege of tumors and can be a potential molecular target for cancer therapy. 

References:

1.        Dunn G.P., et al. Cancer immunoediting: from immunosurveillance to tumor escape, Nature Immunology, 3: 991-998, 2002

2.        Rabinovich G.A., et al. Galectins and their ligands: amplifiers, silencers or turners of a immune response? Trends in Immunology, 23: 313-320, 2002

3.        Rubinstein N. et al. Targeted inhibition of galectin-1 gene expression in tumor cells results in heightened T cell-mediated rejection: A potential mechanism of tumor-immune privilege, Cancer Cell, 5: 241-251, 2004