Extracellular NK histones promote immune cell anti-tumor activity by inducing cell clusters through binding to CD138 receptor
Martín-Antonio, B. (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Suñe, G. (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Najjar, A. (University of Texas. Department of Pediatrics-Research)
Pérez-Amill, Lorena (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Antoñana Vildosola, Asier (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Castellà, Maria (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
León, S. (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Velasco-De Andrés, M. (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Lozano Soto, Francisco (Universitat de Barcelona. Departament de Biomedicina)
Lozano, E. (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Bueno, Clara (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Estanyol, J. M. (Universitat de Barcelona. Facultat de Medicina i Ciències de la Salut)
Munõz-Pinedo, Cristina (Institut d'Investigació Biomèdica de Bellvitge)
Robinson, S. N. (University of Texas. Department of Stem Cell Transplantation and Cellular Therapy)
Urbano Ispizua, Álvaro (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Universitat Autònoma de Barcelona

Data:	2019
Resum:	Background: Natural killer (NK) cells are important anti-tumor cells of our innate immune system. Their anti-cancer activity is mediated through interaction of a wide array of activating and inhibitory receptors with their ligands on tumor cells. After activation, NK cells also secrete a variety of pro-inflammatory molecules that contribute to the final immune response by modulating other innate and adaptive immune cells. In this regard, external proteins from NK cell secretome and the mechanisms by which they mediate these responses are poorly defined. Methods: TRANS-stable-isotope labeling of amino acids in cell culture (TRANS-SILAC) combined with proteomic was undertaken to identify early materials transferred between cord blood-derived NK cells (CB-NK) and multiple myeloma (MM) cells. Further in vitro and in vivo studies with knock-down of histones and CD138, overexpression of histones and addition of exogenous histones were undertaken to confirm TRANS-SILAC results and to determine functional roles of this material transferred. Results: We describe a novel mechanism by which histones are actively released by NK cells early after contact with MM cells. We show that extracellular histones bind to the heparan sulfate proteoglycan CD138 on the surface of MM cells to promote the creation of immune-tumor cell clusters bringing immune and MM cells into close proximity, and thus facilitating not only NK but also T lymphocyte anti-MM activity. Conclusion: This study demonstrates a novel immunoregulatory role of NK cells against MM cells mediated by histones, and an additional role of NK cells modulating T lymphocytes activity that will open up new avenues to design future immunotherapy clinical strategies.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Cell-cell communication ; Histones ; Immunotherapy ; NK cells ; Multiple myeloma
Publicat a:	Journal for immunotherapy of cancer, Vol. 7 Núm. 1 (16 2019) , p. 259, ISSN 2051-1426

DOI: 10.1186/s40425-019-0739-1
PMID: 31619273

16 p, 7.8 MB

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Documents de recerca > Documents dels grups de recerca de la UAB > Centres i grups de recerca (producció científica) > Ciències de la salut i biociències > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Institut de Recerca contra la Leucèmia Josep Carreras
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