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

PloS One
Felicity C StarkLakshmi Krishnan

Abstract

Central 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 antig...Continue Reading

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Citations

Mar 5, 2014·Hematology/oncology Clinics of North America·Marilyn J Telen
Jun 14, 2013·Oncoimmunology·Erika VacchelliLorenzo Galluzzi
Mar 28, 2017·Laboratory Investigation; a Journal of Technical Methods and Pathology·Robert SacksteinSteven R Barthel
Jan 17, 2019·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Gheath AlatrashElizabeth A Mittendorf

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Methods Mentioned

BETA
Fluorescence
density gradient centrifugation
flow cytometry
transgenic

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