The innate immune response to tumors and its role in the induction of T-cell immunity.
Recent genetic studies have resurrected the concept that the adaptive and innate immune systems play roles in tumor surveillance. Natural killer (NK) cells recognize many tumor cells but not normal self cells, and they are thought to aid in the elimination of nascent tumors. Two main strategies are employed by NK cells to recognize tumor targets. Many tumor cells down-regulate class I major histocompatibility complex (MHC) molecules, thus releasing the NK cell from the inhibition provided by class I MHC-specific inhibitory receptors ('missing self recognition'). More recently, it has become clear that a stimulatory receptor expressed by NK cells, T cells and macrophages (NKG2D) recognizes ligands (MHC class I chain related [MIC], H6O, retinoic acid early inducible [Rae1] and UL16 binding proteins [ULBP]) that are up-regulated on tumor cells and virally infected cells but are not expressed well by normal cells. Ectopic expression of these ligands on tumor cells leads to the potent rejection of the tumors in vivo. Importantly, mice that previously rejected the ligand+ tumor cells develop T-cell immunity to the parental (ligand-) tumor cells. The recognition of induced-self ligands as a strategy to recognize abnormal self sets a precedent for a new immune recognition strategy of the innate immune system.
Diefenbach
Andreas
A
Department of Molecular and Cell Biology and Cancer Research Laboratory, University of California, Berkeley, CA 94720, USA.
Raulet
David H
DH
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D007113:Immunity, Innate; D007121:Immunocompetence; D007157:Immunologic Surveillance; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D018448:Models, Immunological; D055655:NK Cell Lectin-Like Receptor Subfamily K; D009368:Neoplasm Transplantation / Q000276:immunology; D009369:Neoplasms / Q000276:immunology*; D011971:Receptors, Immunologic / Q000276:immunology; D055607:Receptors, Natural Killer Cell; D017634:Self Tolerance / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014412:Tumor Virus Infections / Q000276:immunology
D000951:Antigens, Neoplasm; D015395:Histocompatibility Antigens Class I; C527085:KLRK1 protein, human; C527086:Klrk1 protein, mouse; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell