RT Journal Article
T1 Monocyte-Derived Dendritic Cells Differentiated in the Presence of Lenalidomide Display a Semi-Mature Phenotype, Enhanced Phagocytic Capacity, and Th1 Polarization Capability
A1 López Relaño, Juan
A1 Martín Adrados, Beatriz
A1 Real Arévalo, Irene
A1 Lozano Bartolomé, Javier
A1 Abós, Beatriz
A1 Sánchez Ramón, Silvia María
A1 Alonso, Bárbara
A1 Gómez Del Moral Martín-Consuegra, Manuel María
A1 Martínez Naves, Eduardo
AB Lenalidomide is an analog of thalidomide, with potent anticancer activity demonstrated in several hematological malignancies. It has immunomodulatory properties, being able to enhance the activation of different types of immune cells, which results in antitumor activities. Dendritic cells (DCs) are pivotal in the immune response, and different immunotherapeutic approaches targeting these cells are being developed. Since little is known about the effect of lenalidomide on DCs, the goal of the present work was to investigate the phenotype and function of human monocyte-derived DCs differentiated in the presence of lenalidomide (L-DCs). Our results showed that L-DCs display a unique phenotype, with increased cell surface expression of some maturation markers such as CD1d, CD83, CD86, and HLA-DR. This phenotype correlates with a lower expression of the E3 ubiquitin-ligase MARCH-I in L-DCs, upregulating the cell surface expression of CD86 and HLA-DR. In addition, immature L-DCs express higher amounts of DC-SIGN on the cell surface than control immature DCs. After LPS stimulation, production of IL-6 and TNF-α was severely decreased, whereas IL-12 and IL-10 secretion was dramatically upregulated in L-DCs, compared to that in the controls. Functionally, L-DCs are more effectively recognized by NKT cells in cytotoxicity experiments. Furthermore, L-DCs display higher opsonin-independent antigen uptake capability than control DCs. Mixed lymphocyte reaction experiments showed that L-DCs could stimulate naïve CD4 T-cells, polarizing them toward a predominant Th1 phenotype. In summary, DCs derived from monocytes in the presence of lenalidomide present a semi-mature phenotype, increased phagocytic capacity, reduced production of proinflammatory cytokines, and the ability to polarize T-cells toward predominant Th1-type responses; these are qualities that might be useful in the development of new immunotherapeutic treatments.
PB Frontiers Media
SN 1664-3224
YR 2018
FD 2018-06-13
LK https://hdl.handle.net/20.500.14352/92259
UL https://hdl.handle.net/20.500.14352/92259
LA eng
NO López-Relaño J, Martín-Adrados B, Real-Arévalo I, Lozano-Bartolomé J, Abós B, Sánchez-Ramón S, Alonso B, Gómez Del Moral M, Martínez-Naves E. Monocyte-Derived Dendritic Cells Differentiated in the Presence of Lenalidomide Display a Semi-Mature Phenotype, Enhanced Phagocytic Capacity, and Th1 Polarization Capability. Front Immunol. 2018 Jun 13;9:1328. doi: 10.3389/fimmu.2018.01328
NO Ministerio de Economía y Competitividad
NO Universidad Complutense de Madrid
DS Docta Complutense
RD 30 sept 2024