Natural killer cells require selectins for suppression of subcutaneous tumors.
Natural killer (NK) cells recognize and destroy cancer cells through a variety of mechanisms. They may also modulate the adaptive immune response to cancer by interacting with dendritic cells and T cells. Although NK cells play an important role in tumor suppression, little is known about the mechanisms of their recruitment to tumors. Previously it has been shown that subcutaneous tumor growth is enhanced in mice lacking selectins, a family of cell adhesion molecules that mediate the first step of immune cell entry into tissue from the blood. Here we show that NK cell recruitment to tumors is defective in selectin-deficient mice. In vivo NK cell depletion, either pharmacologic or genetic, leads to enhanced subcutaneous tumor growth, similar to the phenotype observed in the selectin-deficient animals. We also show that although NK cells from selectin-deficient mice appear developmentally normal and are functional in in vitro assays, their in vivo function is impaired. This study reveals a role for selectins in NK cell recruitment to tumors and in regulation of effective tumor immunity.
Sobolev
Olga
O
Howard Hughes Medical Institute, David H. Koch Institute for Integrative Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Stern
Patrick
P
Lacy-Hulbert
Adam
A
Hynes
Richard O
RO
D000230:Adenocarcinoma / Q000276:immunology / Q000473:pathology; D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000276:immunology / Q000473:pathology; D048708:Cell Growth Processes / Q000276:immunology; D005260:Female; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D008546:Melanoma, Experimental / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009374:Neoplasms, Experimental / Q000276:immunology*; D019087:Selectins / Q000276:immunology*
D019087:Selectins