title: Modulation of natural killer cell anti-tumor reactivity by platelets.
abstract: Natural killer (NK) cells may prevent tumor progression and metastasis. Apart from the direct interaction with their targets, NK cell activity is influenced by the reciprocal interplay with other hematopoietic cells. While the interaction of NK cells e.g. with dendritic cells or monocytes/macrophages is well characterized, knowledge regarding their crosstalk with platelets, another central component of the blood, is still fragmentary. However, studies in mice and men clearly document a strong dependence of tumor progression and metastasis on quantitatively and functionally normal platelets. In mice, metastasis is inhibited by thrombocytopenia, and this effect is reversed by additional NK cell depletion, indicating that platelets may 'indirectly' contribute to tumor dissemination by impairing NK cell anti-tumor reactivity. In humans, circumstantial evidence indicates that metastasizing malignant cells do not travel through the blood alone, but efficiently attract and get coated by platelets, thereby causing release of platelet granule content. Beyond this secretion of various growth factors and cytokines/chemokines, platelets may also influence NK cell function by immunoregulatory molecules expressed on the platelet surface. Here, we review the available data regarding tumor-platelet-NK cell interaction focusing on metastatic tumor spread and discuss the molecular mechanisms underlying this trilateral crosstalk.
authors.affiliation: Department of Hematology/Oncology, Eberhard Karls University, Tübingen, Germany.
authors.forename: Theresa
authors.initials: T
authors.lastname: Placke
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Kopp
authors.forename: Helmut Rainer
authors.initials: HR
authors.lastname: Salih
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D009362:Neoplasm Metastasis / Q000276:immunology / Q000473:pathology; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D013045:Species Specificity