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https://doi.org/10.1080/2162402X.2015.1093721
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Título: | Overexpression of KIR inhibitory ligands (HLA-I) determines that immunosurveillance of myeloma depends on diverse and strong NK cell licensing |
Fecha de publicación: | 8-abr-2016 |
Editorial: | Taylor and Francis Group |
Cita bibliográfica: | Oncoinmmunology 2016, Vol.5, n.4 |
ISSN: | Print: 2162-4011 Electronic: 2162-402X |
Palabras clave: | HLA-C HLA-I KIR KIR ligands |
Resumen: | Missing self recognition makes cancer sensitive to natural killer cell (NKc) reactivity. However, this model disregards the NKc licensing effect, which highly increases NKc reactivity through interactions of inhibitory killer cell immunoglobulin-like receptors (iKIR) with their cognate HLA-I ligands. The influence of iKIR/HLA-ligand (HLA-C1/C2) licensing interactions on the susceptibility to and progression of plasma cell (PC) dyscrasias was evaluated in 164 Caucasian patients and 286 controls. Compared to controls, myeloma accumulates KIR2DL1−L2+L3− genotypes (2.8% vs. 13.2%, p < 0.01, OR = 5.29) and less diverse peripheral repertoires of NKc clones. Less diverse and weaker-affinity repertoires of iKIR2D/HLA-C licensing interactions increased myeloma susceptibility. Thus, the complete absence of conventional iKIR2D/HLA-C licensing interactions (KIR2DL1−L2+L3−/C2C2, 2.56% vs. 0.35%; p < 0.05; OR = 15.014), single-KIR2DL3+/C1+ (20.51% vs. 10.84%; p < 0.05; OR = 2.795) and single-KIR2DL2+/C1+ (12.82% vs. 4.9%; p < 0.01; OR = 5.18) interactions were over-represented in myeloma, compared to controls. Additionally, KIR2DL1−L2+L3− (20% vs. 83%, p < 0.00001) as well as KIR3DL1− (23% vs. 82%, p < 0.00001) genotypes had a dramatic negative impact on the 3-y progression-free survival (PFS), particularly in patients with low-tumor burden. Remarkably, myeloma-PCs, compared to K562 and other hematological cancers, showed substantial over-expression of HLA-I (“increasing-self” instead of missing-self), including HLA-C, and mild expression of ligands for NKc activating receptors (aRec) CD112, CD155, ULBP-1 and MICA/B, which apparently renders myeloma-PCs susceptible to lysis mainly by licensed NKc. KIR2DL1−L2+L3−/C2C2 patients (with no conventional iKIR2D/HLA-C licensing interactions) lyse K562 but barely lyse myeloma-PCs (4% vs. 15%; p < 0.05, compared to controls). These results support a model where immunosurveillance of no-missing-self cancers, e.g., myeloma, mainly depends on NKc licensing. |
Autor/es principal/es: | Martínez Sánchez, María V. Periago, Adela Legaz Pérez, Isabel Gimeno, Lourdes Mrowiec, Anna Montes Baqueros, Natividad R. Campillo, Jose Antonio Bolarin, José M. Bernardo, María V. López Álvarez, María R. González, Consuelo García Caray, María C. Muro, Manuel Cabañas Perianes, Valentín Fuster, Jose L. García Alonso, Ana M. Moraleda, José M. Álvarez López, María Rocio Minguela, Alfredo |
Facultad/Departamentos/Servicios: | Facultades, Departamentos, Servicios y Escuelas::Departamentos de la UMU::Ciencias Sociosanitarias |
Versión del editor: | https://www.tandfonline.com/doi/full/10.1080/2162402X.2015.1093721 |
URI: | http://hdl.handle.net/10201/143023 |
DOI: | https://doi.org/10.1080/2162402X.2015.1093721 |
Tipo de documento: | info:eu-repo/semantics/article |
Número páginas / Extensión: | 12 |
Derechos: | info:eu-repo/semantics/openAccess Atribución-NoComercial 4.0 Internacional |
Descripción: | © 2016 Taylor & Francis Group, LLC. This manuscript version is made available under the CC-BY-NC 4.0 license http://creativecommons.org/licenses/by-nc/4.0/. This document is the Published version of a Published Work that appeared in final form in OncoImmunology. To access the final edited and published work see https://doi.org/10.1080/2162402X.2015.1093721 |
Aparece en las colecciones: | Artículos: Ciencias Sociosanitarias |
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