title: NKG2D-NKG2D Ligand Interaction Inhibits the Outgrowth of Naturally Arising Low-Grade B Cell Lymphoma In Vivo.
abstract: It is now clear that recognition of nascent tumors by the immune system is critical for survival of the host against cancer. During cancer immunoediting, the ability of the tumor to escape immune recognition is important for tumor development. The immune system recognizes tumors via the presence of classical Ags and also by conserved innate mechanisms. One of these mechanisms is the NKG2D receptor that recognizes ligands whose expression is induced by cell transformation. In this study, we show that in NKG2D receptor-deficient mice, increasing numbers of B cells begin to express NKG2D ligands as they age. Their absence in wild-type mice suggests that these cells are normally cleared by NKG2D-expressing cells. NKG2D-deficient mice and mice constitutively expressing NKG2D ligands had increased incidence of B cell tumors, confirming that the inability to clear NKG2D ligand-expressing cells was important in tumor suppression and that NKG2D ligand expression is a marker of nascent tumors. Supporting a role for NKG2D ligand expression in controlling the progression of early-stage B cell lymphomas in humans, we found higher expression of a microRNA that inhibits human NKG2D ligand expression in tumor cells from high-grade compared with low-grade follicular lymphoma patients.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110;
authors.forename: Saravanan
authors.identifier: 0000-0001-8904-8497
authors.initials: S
authors.lastname: Raju
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110;
authors.forename: Lena Z
authors.initials: LZ
authors.lastname: Kretzmer
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110;
authors.forename: Olivia I
authors.initials: OI
authors.lastname: Koues
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110;
authors.forename: Jacqueline E
authors.identifier: 0000-0001-8832-3661
authors.initials: JE
authors.lastname: Payton
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110;
authors.forename: Eugene M
authors.initials: EM
authors.lastname: Oltz
authors.affiliation: Department of Medicine, Washington University School of Medicine, St. Louis, MO 63105;
authors.forename: Amanda
authors.identifier: 0000-0001-6809-4566
authors.initials: A
authors.lastname: Cashen
authors.affiliation: Department of Histology and Embryology, Medical Faculty University of Rijeka, 51000 Rijeka, Croatia;
authors.forename: Bojan
authors.identifier: 0000-0003-3930-9630
authors.initials: B
authors.lastname: Polic
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110;
authors.forename: Robert D
authors.initials: RD
authors.lastname: Schreiber
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110; Howard Hughes Medical Institute, Washington University School of Medicine, St Louis, MO 63110; and shawa6@gene.com.
authors.forename: Andrey S
authors.initials: AS
authors.lastname: Shaw
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110; Department of Microbiology, Molecular Genetics, and Immunology, University of Kansas Medical Center, Kansas City, KS 66160.
authors.forename: Mary A
authors.identifier: 0000-0001-5685-8573
authors.initials: MA
authors.lastname: Markiewicz
mesh_terms: D000818:Animals; D018450:Disease Progression; D006801:Humans; D008024:Ligands; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: C527086:Klrk1 protein, mouse; D008024:Ligands; D035683:MicroRNAs; D055655:NK Cell Lectin-Like Receptor Subfamily K