RT Journal Article
T1 Mesenchymal stem cells derived from low risk acute lymphoblastic leukemia patients promote NK cell antitumor activity
A1 Entrena Martínez, Ana
A1 Varas, Alberto
A1 Vázquez, Miriam
A1 Melen, Gustavo J.
A1 Fernández Sevilla, Lidia M.
A1 García Castro, Javier
A1 Ramírez, Manuel
A1 Zapata González, Agustín Gregorio
A1 Vicente, Ángeles
AB Mesenchymal stem cells (MSCs) are key components of the bone marrow microenvironment which contribute to the maintenance of the hematopoietic stem cell niche and exert immunoregulatory functions in innate and adaptive immunity. We analyze the immunobiology of MSCs derived from acute lymphoblastic leukemia (ALL) patients and their impact on NK cell function. In contrast to the inhibitory effects on the immune response exerted by MSCs from healthy donors (Healthy-MSCs), we demonstrate that MSCs derived from low/intermediate risk ALL patients at diagnosis (ALL-MSCs) promote an efficient NK cell response including cytokine production, phenotypic activation and most importantly, cytotoxicity. Longitudinal studies indicate that these immunostimulatory effects of ALL-MSCs are progressively attenuated. Healthy-MSCs adopt ALL-MSC-like immunomodulatory features when exposed to leukemia cells, acquiring the ability to stimulate NK cell antitumor function. The mechanisms underlying to these functional changes of ALL-MSCs include reduced production of soluble inhibitory factors, differential expression of costimulatory and coinhibitory molecules, increased expression of specific TLRs and Notch pathway activation. Collectively our findings indicate that, in response to leukemia cells, ALL-MSCs could mediate a host beneficial immunomodulatory effect by stimulating the antitumor innate immune response.
PB Elsevier
SN 0304-3835
YR 2015
FD 2015-07-28
LK https://hdl.handle.net/20.500.14352/23230
UL https://hdl.handle.net/20.500.14352/23230
LA eng
NO Ministerio de Economía y Competitividad (MINECO)
NO Comunidad de Madrid
NO Asociación Española contra el Cáncer 2010
NO Instituto de Salud Carlos III (España)
DS Docta Complutense
RD 7 may 2024