Lack of functional selectin ligand interactions compromises long term tumor protection by CD8 + T cells

  1. Get@NRC: Lack of functional selectin ligand interactions compromises long term tumor protection by CD8 + T cells (Opens in a new window)
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Journal titlePLoS ONE
Article numbere32211
Subjectbacterial vaccine; gamma interferon; selectin; tumor antigen; fucosyltransferase; ligand; ovalbumin; selectin; animal cell; animal experiment; animal model; article; cancer prevention; CD8+ T lymphocyte; cell infiltration; cell migration; cell proliferation; cellular immunity; controlled study; dendritic cell; in vivo study; Listeria monocytogenes; lymphocyte function; mouse; nonhuman; phenotype; protein determination; protein expression; protein function; protein localization; protein protein interaction; tumor growth; tumor immunity; tumor xenograft; wild type; animal; antigen presentation; immunology; mouse mutant; neoplasm; Animals; Antigen Presentation; CD8-Positive T-Lymphocytes; Fucosyltransferases; Ligands; Mice; Mice, Knockout; Neoplasms; Ovalbumin; Selectins
AbstractCentral memory CD8 + T cells expressing the adhesion molecule CD62L (L-selectin) are potent mediators of anti-cancer immunity due to their ability to proliferate extensively upon antigen re-stimulation. The interaction of selectin with its ligands mediates leukocyte rolling along high endothelial venules. Mice deficient in α(1,3) Fucosyltransferase IV and VII (FtDKO) lack functional L, P and E selectin ligands. Thus, we addressed whether the lack of selectin ligand interactions alters tumor protection by CD8 + T cells in FtDKO mice. Listeria monocytogenes-OVA (LM-OVA) infection evoked potent OVA-specific CD8 + T cells that proliferated and contracted at similar kinetics and phenotype in FtDKO and wild-type mice. Additionally, OVA-specific CD8 + T cells in both mouse strains exhibited similar phenotypic differentiation, in vivo cytolytic activity and IFN-γ expression. However, FtDKO mice succumbed to B16-OVA tumors significantly earlier than wild-type mice. In contrast, FtDKO mice evoked strong recall memory CD8 + T cell responses and protection to systemic LM-OVA re-challenge. The diminished tumor protection in FtDKO mice was not related to defective antigen presentation by dendritic cells or reduced proliferation of antigen-specific CD8 + T cells. However, WT or FtDKO OVA-specific CD8 + T cells showed significantly reduced ability to traffic to lymph nodes upon adoptive transfer into naïve FtDKO recipients. Furthermore, FtDKO OVA-specific CD8 + T cells displayed poor ability to infiltrate tumors growing in WT mice. These results reveal that selectin ligand expression on host endothelium as well CD8 + T cells may be important for their efficient and continued extravasation into peripheral tumors. © 2012 Stark et al.
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AffiliationNational Research Council Canada (NRC-CNRC); NRC Institute for Biological Sciences (IBS-ISB)
Peer reviewedYes
NPARC number21269270
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Record identifier0a3dfeaa-b4d3-4bde-bf82-e7a66eed9050
Record created2013-12-12
Record modified2016-05-09
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