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Galectin-1 research in T cell immunity: past, present and future.

ABSTRACT: Galectin-1 (Gal-1) is one of 15 evolutionarily conserved ß-galactoside-binding proteins that display biologically-diverse activities in pathogenesis of inflammation and cancer. Gal-1 is variably expressed on immune cells and endothelial cells, though is commonly found and secreted at high levels in cancer cells. It induces apoptosis in effector T cells through homodimeric binding of N-acetyllactosamines on membrane glycoproteins (Gal-1 ligands). There is also compelling evidence in models of cancer and autoimmunity that recombinant Gal-1 (rGal-1) can potentiate immunoregulatory function of T cells. Here, we review Gal-1's structural and functional features, while analyzing potential drawbacks and technical difficulties inherent to rGal-1's nature. We also describe new Gal-1 preparations that exhibit dimeric stability and functional activity on T cells, providing renewed excitement for studying Gal-1 efficacy and/or use as anti-inflammatory therapeutics. We lastly summarize strategies targeting the Gal-1-Gal-1 ligand axis to circumvent Gal-1-driven immune escape in cancer and boost anti-tumor immunity.

SUBMITTER: Cedeno-Laurent F

PROVIDER: S-EPMC3266984 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature

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Galectin-1 research in T cell immunity: past, present and future.

Cedeno-Laurent Filiberto F Dimitroff Charles J CJ

Clinical immunology (Orlando, Fla.) 20111006 2

Galectin-1 (Gal-1) is one of 15 evolutionarily conserved ß-galactoside-binding proteins that display biologically-diverse activities in pathogenesis of inflammation and cancer. Gal-1 is variably expressed on immune cells and endothelial cells, though is commonly found and secreted at high levels in cancer cells. It induces apoptosis in effector T cells through homodimeric binding of N-acetyllactosamines on membrane glycoproteins (Gal-1 ligands). There is also compelling evidence in models of can ...[more]

PMID: 22019770

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Project description:Hamster polyomavirus (Mesocricetus auratus polyomavirus 1, HaPyV) was discovered as one of the first rodent polyomaviruses at the end of the 1960s in a colony of Syrian hamsters (Mesocricetus auratus) affected by skin tumors. Natural HaPyV infections have been recorded in Syrian hamster colonies due to the occurrence of skin tumors and lymphomas. HaPyV infections of Syrian hamsters represent an important and pioneering tumor model. Experimental infections of Syrian hamsters of different colonies are still serving as model systems (e.g., mesothelioma). The observed phylogenetic relationship of HaPyV to murine polyomaviruses within the genus Alphapolyomavirus, and the exclusive detection of other cricetid polyomaviruses, i.e., common vole (Microtus arvalis polyomavirus 1) and bank vole (Myodes glareolus polyomavirus 1) polyomaviruses, in the genus Betapolyomavirus, must be considered with caution, as knowledge of rodent-associated polyomaviruses is still limited. The genome of HaPyV shows the typical organization of polyomaviruses with an early and a late transcriptional region. The early region encodes three tumor (T) antigens including a middle T antigen; the late region encodes three capsid proteins. The major capsid protein VP1 of HaPyV was established as a carrier for the generation of autologous, chimeric, and mosaic virus-like particles (VLPs) with a broad range of applications, e.g., for the production of epitope-specific antibodies. Autologous VLPs have been applied for entry and maturation studies of dendritic cells. The generation of chimeric and mosaic VLPs indicated the high flexibility of the VP1 carrier protein for the insertion of foreign sequences. The generation of pseudotype VLPs of original VP1 and VP2-foreign protein fusion can further enhance the applicability of this system. Future investigations should evaluate the evolutionary origin of HaPyV, monitor its occurrence in wildlife and Syrian hamster breeding, and prove its value for the generation of potential vaccine candidates and as a gene therapy vehicle.

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Galectin-1 research in T cell immunity: past, present and future.

Publications

Galectin-1 research in T cell immunity: past, present and future.

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